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Chapter 6 : Macrophages and Other Cells in Tuberculous Lesions

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Macrophages and Other Cells in Tuberculous Lesions, Page 1 of 2

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Abstract:

The main types of cells participating in rabbit tuberculous lesions are dendritic cells (DCs), macrophages, natural killer (NK) cells, lymphocytes, and granulocytes. Follicular DCs and antigen-activated helper T cells interact with B cells for antibody production. The primary acquired immune response to the tubercle bacillus is initiated by DCs that activate T cells. Macrophages can inhibit or kill intracellular tubercle bacilli by means of reactive nitrogen and oxygen intermediates (RNIs and ROIs), to which M. tuberculosis is exquisitely susceptible. Tubercle bacilli can live for months in mouse granulomas without multiplying and without dying. Macrophages are the major cells of the mononuclear phagocyte system. This system is composed of promonocytes in the bone marrow, monocytes in the circulation, and macrophages in the tissues. Active collagenase (an enzyme secreted but not stored in macrophages) was only detected in fluids from peak BCG lesions. T lymphocytes have been divided into various subsets by their CD4 and CD8 surface antigens, by their functions (T helper [Th] cells, regulatory T cells, and cytotoxic T cells), and by the cytokines they produce (Th1 and Th2). Perforin is a protein that can polymerize to form a hole (or pore) in the target cell’s membrane. The eosinophils in rabbit BCG lesions seem to show higher ribonuclease activity than any other cell present. At sites of many infections, mast cell cytokines have been found to enhance the recruitment of T cells. They probably play a similar role in lesions produced by the tubercle bacillus.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Figures

Image of FIGURE 1
FIGURE 1

Viable counts and total counts of virulent tubercle bacilli (H37Rv) in the lungs of mice from 9 to 25 weeks after an intravenous infection. After the lungs were homogenized, the viable counts were calculated from the CFU developing on plates containing solid culture medium. The total counts were calculated from the bacilli observed microscopically on spread-smears after acid-fast staining. During this time period, one of the four groups of mice received isoniazid-pyrazinamide (PZA/INH) daily to kill the bacilli.

Note that for untreated mice the average total counts were 0.3 to 0.4 logs higher (2.0 to 2.5 times) than the average viable counts, and that PZA/INH treatment markedly reduced the viable counts but had relatively little effect on the total counts. These findings indicate that (i) most of the dead tubercle bacilli persisted in mouse lungs for many weeks; (ii) most of the live bacilli were in a “dormant” nonmultiplying state, because if they had been multiplying and then had been killed, the total counts (including the dead bacilli) would have increased; and (iii) the good CMI developed by mice activated macrophages sufficiently to prevent the intracellular multiplication of most of the tubercle bacilli. However, at least some of the bacilli were not inhibited by this good CMI, because the disease progressed until the mice succumbed. In other words, not all of the bacilli were dormant, and some bacillary multiplication occurred.

Redrawn from reference 73. These results were confirmed in reference 74 using quantitative real-time PCR technology.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 2
FIGURE 2

(A) Size of 48-h tuberculin reactions. (B) Size of BCG lesions. (C) Weighted number of activated β-galactosidase-positive macrophages, just below the surface of the chamber beds of BCG lesions (closed circles) and 72-h tuberculin reactions (open circles). To obtain the weighted number of β-galactosidase-positive macrophages, the number of + cells was multiplied by 1, ++ cells were multiplied by 2, +++ cells were multiplied by 3, and ++++ cells were multiplied by 4, and then the products were added together. Reproduced with permission from reference 108.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 3
FIGURE 3

Chamber bed of a 32-day BCG lesion. Many darkly staining +++ and ++++ β-galactosidase-positive macrophages are present. A thin proteinaceous layer covers the surface of the chamber bed. Stained with 5-bromo-4-chloro-3-indolyl-β--galactoside, hematoxylin and eosin. Magnification, ×30. Reproduced with permission from reference 108.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 4
FIGURE 4

Lysozyme, RNase, DNase, and lactic dehydrogenase (LDH) activities in the chamber fluids of BCG lesions of various ages (closed circles and line graph), 1-day tuberculin reactions (open circles), and normal skin controls (shaded horizontal lines). Lysozyme is both secreted and stored; RNase and DNase are released on cell death and possibly regurgitated, but not secreted; and LDH is released only on cell death.

The chambers were glued to the still intact skin around the area where the epidermis was removed. They were then filled with HEPES culture medium 199, and the fluid within the chambers was collected 48 h later. Note that the highest level of these extracellular hydrolases occurred when tuberculin sensitivity had developed, the BCG lesions were growing to peak size, and the greatest number of activated macrophages was in the chamber bed (see Fig. 1). Reproduced with permission from reference 108.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 5
FIGURE 5

Tissue section of a 14-day rabbit skin lesion produced by the intradermal injection of 60 × 106 polystyrene latex particles. This lesion showed no inflammation. All of the polystyrene particles were within macrophages staining ++ to ++++ for β-galactosidase. Note that the dermal collagen fibers adjacent to the macrophages are intact, suggesting that no effective collagenase was produced by these cells. A small amount of collagenase was found at 48 h in fluids within chambers placed over the polystyrene lesions, but 2 to 3 times this amount of collagenase was found in chamber fluids placed over 14-day BCG lesions, where the collagen fibers were hydrolyzed (108). Stained with 5-bromo-4-chloro-3-indolyl-β--galactoside, hematoxylin and eosin. Magnification, ×350. Reproduced with permission from reference 108.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 6
FIGURE 6

Estimates of the total amount of each of four enzymes in tissue sections of dermal BCG lesions during their development and healing. The mononuclear cells (mostly macrophages) in these tissue sections were single-stained for acid phosphatase, cathepsin D, esterase and β-galactosidase and were evaluated microscopically at both 35× and 125× magnifications. For quantitation, both the distribution and intensity of the histochemically produced color were taken into account. Then, the total amount of staining was given a rating on a 0 to 9 scale. The standard errors of the means are shown.

Note that the total amount of each enzyme was greatest when the lesions peaked in size (Fig. 2B), and the levels of each enzyme more or less rose and fell in parallel during the development and healing of the lesions. Reproduced with permission from reference 82.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 7
FIGURE 7

Distribution of mononuclear cells (MN) (mostly macrophages) that single-stained for acid phosphatase, cathepsin D, β-galactosidase, or esterase in developing, peak, and healing dermal BCG lesions. The percentage of MN staining + to ++++ was evaluated microscopically at the edge of the caseous necrotic center, in the viable tissue near this center, and more peripherally in representative high-power fields at ×500 magnification. The standard errors of the means are shown.

Note that macrophages containing β-galactosidase and esterase were more frequent near the caseous center (A and B), and macrophages containing acid phosphatase and cathepsin D were more frequent in the peripheral regions (C). These findings quantitatively demonstrate the “macrolocal” distribution of activated macrophages within tuberculous lesions (see text). Reproduced with permission from reference 82.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 8
FIGURE 8

Distribution of activated mononuclear cells (mainly macrophages) in double-stained tissue sections of developing, peak, and healing rabbit dermal BCG lesions. These sections were stained histochemically for pairs of enzymes: one red and one blue. The red enzymes were acid phosphatase, cathepsin D, or red esterase. The blue enzymes were β-galactosidase or blue esterase. The mononuclear cells were counted microscopically at the edge of the caseous necrotic center (A), in the viable tissue near this necrosis (B), and in peripheral areas of the lesion (C).

The length of the bars represents 100% of the mononuclear cells in each area. The cells that stained for only one enzyme of the pair were either red (stippled bars) or blue (hatched bars). The cells that stained for both enzymes of the pair were purple (black bars).

The black bars in column 3 and the mirror-image patterns C:B:A and A:B:C in columns 1 and 2 show that the same macrophage population contained β-galactosidase, red esterase, and blue esterase. Macrophages containing cathepsin D and acid phosphatase had similar distributions (see columns 1 and 2), but since they both stained red, they could not be differentiated in the same tissue section. (The red esterase is from a diazo dye; the blue esterase is from an indolyl dye [82].)

These graphs confirm the microlocal mononuclear cell activation shown in Color Plate 2, i.e., that some macrophages almost always stain for an enzyme different from that of the majority of macrophages in a given area.

Reproduced with permission from reference 82.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 9
FIGURE 9

Tissue section of a 21-day rabbit dermal BCG lesion stained for β-galactosidase, our marker enzyme for macrophage activation. A group of epithelioid cells with high enzyme activity is seen in the tuberculous granulation tissue that surrounds the lesion’s liquefied caseous center (in the lower right corner of the photograph). Mature epithelioid cells (identified by their rounded appearance) stain the strongest (+++ and ++++) for β-galactosidase. These activated macrophages cluster in the area of the BCG lesion where the bacilli (identified by acid-fast staining) are located. Stained with 5-bromo-4-chloro-3-indolyl-β--galactoside, lightly counterstained with hematoxylin. Magnification, ×200. Reproduced with permission from reference 80.

This picture clearly demonstrates the principle of local immunity, i.e., the bacilli and their products stimulate local lymphocytes to produce cytokines that activate nearby macrophages. Highly activated macrophages are known to contain high concentrations of reactive oxygen and nitrogen intermediates and hydrolytic enzymes that kill or inhibit the tubercle bacillus. Such highly activated macrophages may be harmful to tissues, especially if they die and release their contents. Therefore, the host apparently limits the activation of macrophages to local sites of bacillary lodgement where they are most needed to control the infection.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 10
FIGURE 10

Tissue section of a 33-day rabbit dermal BCG lesion stained for cytochrome oxidase, an enzyme involved in oxygen metabolism. The large cells are epithelioid cells, similar to those in Fig. 9. The most mature ones with the rounded appearance stain the darkest. In other words, the macrophages most effective in inhibiting the intracellular growth of the tubercle bacillus contained the highest levels of both hydrolytic and oxidative enzymes. The other cells (which we cannot differentiate) are probably small macrophages, dendritic cells, lymphocytes, and plasma cells. Stained with 8-amino-1,2,3,4-tetrahydroquinoline and p-aminodiphenylamine (84) with no counterstain, so the cell nuclei stain lighter than the cytoplasm. Magnification, ×470. Reproduced with permission from reference 81.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 11
FIGURE 11

A generalized presentation of the common types of T cells, i.e., those with αβ antigen receptors (see reference 1). Note that T cells with the CD4 and CD8 surface markers can produce similar cytokines.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 12
FIGURE 12

Percentage of mononuclear cells (MN) (mostly lymphocytes) immunostained for CD4 (A) or CD8 (B) in primary and reinfection BCG lesions and in tuberculin reactions. At 2 days, the reinfection BCG lesions and the tuberculin reactions contained a higher percentage of CD8 cells than did the primary lesions, suggesting that tuberculin sensitivity increases the number of cytotoxic CD8 cells in tuberculous lesions. Note, however, that CD4 cells are always much more numerous than CD8 cells (compare the y axes).

Each point represents the mean of four lesions with its standard error. For reinfection BCG lesions versus primary BCG lesions: *P < 0.05 and **P < 0.01; for tuberculin reactions versus primary BCG lesions: † P < 0.05; and for reinfection BCG lesions versus tuberculin reactions: ‡ P < 0.05 and ‡‡ P < 0.01. Reproduced with permission from reference 119.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 13
FIGURE 13

Mononuclear cells (MN) and granulocytes (PMN) per mm2 of tissue section in BCG lesions at various times during their development and healing. The mononuclear cells were mostly macrophages with some medium and large lymphocytes (and probably some dendritic cells). In the BCG lesions, only the areas that were densely infiltrated with cells were counted. These areas were usually found about one-third of the distance from the edge of the caseous center to the edge of the lesion. PMN were even more numerous nearer the caseous center. At 37 days, the BCG lesions were much smaller, so the total number of cells present was much reduced. Reproduced with permission from reference 163.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 14
FIGURE 14

A tissue section of a 19-day rabbit dermal BCG lesion incubated on a film of RNA for 1 h at 23°C and stained with toluidine blue. Note the “starry sky” appearance representing RNase activity in a percentage of the granulocytes. The cells that have digested the substrate film beneath the tissue section were probably eosinophils, because eosinophils are known to contain high levels of RNase (181, 182), and because most of the PMN (recognized by their multilobed nucleus) were inactive. Magnification, ×180. Reproduced with permission from reference 81.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 15
FIGURE 15

A postcapillary venule in a guinea pig contact-sensitivity reaction to dinitrochlorobenzene. Note the preservation of three basophils (arrows): one just outside the venule, one inside the venule, and one between the endothelium and its basement membrane. In this thin GMA tissue section, endothelial cells and pericytes can be easily distinguished by their location. In other words, these thin plastic-embedded tissue sections enable a resolution with light microscopy that approaches the resolution with low-power electron microscopy. In guinea pigs, rabbits, and humans, mast cells and basophils can be easily distinguished by their shape and staining characteristics (164). The tissue specimen was embedded in GMA, cut at 1 to 2 μm, and stained with Giemsa. Magnification, ×790. Reproduced with permission from reference 164.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 16
FIGURE 16

Mast cells in a tissue section of normal rabbit skin. The tissue specimen was “cold-embedded” in GMA (174), cut at 1 to 2 μm, and stained with Giemsa. Magnification, ×900.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 17
FIGURE 17

Activated fibroblasts (+++ to ++ ++) between collagen fibers in the corium of a healing (6-day) rabbit dermal inflammatory lesion (produced by the topical application of 1% sulfur mustard). These fibroblasts were stained histochemically for the lysosomal enzyme acid phosphatase, which produces the bright red color that appears dark in this black-and-white photograph. The high activation of these fibroblasts is indicated by their large size and the large amount of acid phosphatase that they contain. Normal rabbit skin has relatively few activated fibroblasts (179). Activated fibroblasts produce the new collagen and ground substance associated with healing. A small blood vessel containing erythrocytes can be seen in the lower half of the photograph.

Depicted is a 6-μm “cold-embedded” GMA tissue section, stained histochemically with naphthol AS-BI phosphate and fast red violet LB, and counterstained with hematoxylin. Magnification, ×540. Reproduced with permission from reference 179.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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Image of FIGURE 18
FIGURE 18

A 1-day dermal inflammatory lesion that was produced in the skin of a rabbit by topical 1% sulfur mustard in methylene chloride. Note the dilated lymphatic vessel and two adjacent small blood vessels containing erythrocytes. This acute chemically induced lesion was grossly edematous, so the lymphatic vessel was dilated from the excess tissue fluid that it was removing. Depicted is a “cold-embedded” (174) 1- to 2- μm GMA tissue section, stained with Giemsa (164). Magnification, ×600.

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
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References

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1. Janeway, C. A., Jr.,, P. Travers,, M. Walport, and, M. J. Shlomchik. 2001. Immunobiology: the Immune System in Health and Disease, 5th ed. Garland Publishing, New York, N.Y.
2. Dannenberg, A. M., Jr., and, J. F. Tomashefski, Jr. 1998. Pathogenesis of pulmonary tuberculosis, p. 24472471. In A. P. Fishman (ed.), Fishman’s Pulmonary Diseases and Disorders, 3rd ed., vol. 2. McGraw-Hill Co., Inc, New York, N.Y.
3. Banchereau, J., and, R. M. Steinman. 1998. Dendritic cells and the control of immunity. Nature 392:245252.
4. Cella, M.,, F. Sallusto, and, A. Lanzavecchia. 1997. Origin, maturation and antigen presenting function of dendritic cells. Curr. Opin. Immunol. 9:1016.
5. Reid, S. D.,, G. Penna, and, L. Adorini. 2000. The control of T cell responses by dendritic cell subsets. Curr. Opin. Immunol. 12:114121.
6. Schuler, G.,, B. Thurner, and, N. Romani. 1997. Dendritic cells: from ignored cells to major players in T-cell-mediated immunity. Int. Arch. Allergy Immunol. 112:317322.
7. Maldonado-Lopez, R., and, M. Moser. 2001. Dendritic cell subsets and the regulation of Th1/Th2 responses. Semin. Immunol. 13:275282.
8. Moser, M., and, K. M. Murphy. 2000. Dendritic cell regulation of Th1-Th2 development. Nat. Immunol. 1:199205.
9. Arina, A.,, I. Tirapu,, C. Alfaro,, M. Rodriguez-Calvillo,, G. Mazzolini,, S. Inoges,, A. Lopez,, E. Feijoo,, M. Bendandi, and, I. Melero. 2002. Clinical implications of antigen transfer mechanisms from malignant to dendritic cells: exploiting cross-priming. Exp. Hematol. 30:13551364.
10. Bajénoff, M.,, S. Granjeaud, and, S. Guerder. 2003. The strategy of T cell antigen-presenting cell encounter in antigen-draining lymph nodes revealed by imaging of initial T cell activation. J. Exp. Med. 198:715724.
11. Jeurissen, A.,, J. L. Ceuppens, and, X. Bossuyt. 2004. T lymphocyte dependence of the antibody response to “T lymphocyte independent type 2” antigens. Immunology 111:17.
12. Luster, A. D. 2002. The role of chemokines in linking innate and adaptive immunity. Curr. Opin. Immunol. 14:129135.
13. Granucci, F.,, I. Zanoni,, S. Feau, and, P. Ricciardi-Castagnoli. 2003. Dendritic cell regulation of immune responses: a new role for interleukin 2 at the intersection of innate and adaptive immunity. EMBO J. 22:25462551.
14. Brown, K. A.,, P. Bedford,, M. Macey,, D. A. McCarthy,, F. Leroy,, A. J. Vora,, A. J. Stagg,, D.C. Dumonde, and, S. C. Knight. 1997. Human blood dendritic cells: binding to vascular endothelium and expression of adhesion molecules. Clin. Exp. Immunol. 107:601607.
15. Esser, M. T.,, R. D. Marchese,, L. S. Kierstead,, L. G. Tussey,, F. Wang,, N. Chirmule, and, M. W. Washabaugh. 2003. Memory T cells and vaccines. Vaccine 21:419430.
16. Dong, V. M.,, D. H. McDermott, and, R. Abdi. 2003. Chemokines and diseases. Eur. J. Dermatol. 13:224230.
17. Woltman, A. M., and, C. van Kooten. 2003. Functional modulation of dendritic cells to suppress adaptive immune responses. J. Leukoc. Biol. 73:428441.
18. Shi, Y.,, J. E. Evans, and, K. L. Rock. 2003. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425:516521.
19. Matzinger, P. 2002. The danger model: a renewed sense of self. Science 296:301305.
20. Galluci, S., and, P. Matzinger. 2001. Danger signals: SOS to the immune system. Curr. Opin. Immunol. 13:114119.
21. Reis e Sousa, C. 2004. Activation of dendritic cells: translating innate into adaptive immunity. Curr. Opin. Immunol. 16:2125.
22. Chen, L. 2004. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat. Rev. Immunol. 4:336347.
23. Min, W.-P.,, D. Zhou,, T. E. Ichim,, G. H. Strejan,, X. Xia,, J. Yang,, X. Huang,, B. Garcia,, D. White,, P. Dutartre,, A. M. Jevnikar, and, R. Zhong. 2003. Inhibitory feedback loop between tolerogenic dendritic cells and regulatory T cells in transplant tolerance. J. Immunol. 170:13041312.
24. Steinman, R. M.,, D. Hawiger, and, M. C. Nussenzweig. 2003. Tolerogenic dendritic cells. Annu. Rev. Immunol. 21:685711.
25. Morel, P. A.,, M. Feili-Hariri,, P. T. Coates, and, A. W. Thomson. 2003. Dendritic cells, T cell tolerance and therapy of adverse immune reactions. Clin. Exp. Immunol. 133:110.
26. Steptoe, R. J., and, A. W. Thomson. 1996. Dendritic cells and tolerance induction. Clin. Exp. Immunol. 105:397402.
27. Colino, J., and, C. M. Snapper. 2003. Dendritic cells, new tools for vaccination. Microbes Infect. 5:311319.
28. Asselin-Paturel, C., and, G. Trinchieri. 2005. Production of type I interferons: plasmacytoid dendritic cells and beyond. J. Exp. Med. 202:461465.
29. Colonna, M.,, G. Trinchieri, and, Y.-J. Liu. 2004. Plasmacytoid dendritic cells in immunity. Nat. Immunol. 5:12191226.
30. van den Elson, P. J., and, A. Rudensky. 2004. Antigen presentation and recognition: recent developments—an editorial overview. Curr. Opin. Immunol. 16:6366.
31. Gatti, E., and, P. Pierre. 2003. Understanding the cell biology of antigen presentation:the dendritic cell contribution. Curr. Opin. Cell Biol. 15:468473.
32. Kaufmann, S. H. E., and, U. E. Schaible. 2005. Antigen presentation and recognition in bacterial infections. Curr. Opin. Immunol. 17:7987.
33. Sugita, M.,, M. Cernadas, and, M. B. Brenner. 2004. New insights into pathways for CD1-mediated antigen presentation. Curr. Opin. Immunol. 16:9095.
34. Moody, D. B., and, S. A. Porcelli. 2003. Intra-cellular pathways of CD1 antigen presentation. Nat. Rev. Immunol. 3:1122.
35. Brigl, M., and, M. B. Brenner. 2004. CD1: antigen presentation and T cell function. Annu. Rev. Immunol. 22:817890.
36. Van Rhijn, I.,, D. M. Zajonc,, I. A. Wilson, and, D. B. Moody. 2005. T-cell activation by lipopep-tide antigens. Curr. Opin. Immunol. 17:222229.
37. Calabi, F.,, J. M. Jarvis,, L. Martin, and, C. Milstein. 1989. Two classes of CD1 genes. Eur. J. Immunol. 19:285292.
38. Roura-Mir, C.,, L. Wang,, T.-Y. Cheng,, I. Matsunaga,, C. C. Dascher,, S. L. Peng,, M. J. Fenton,, C. Kirschning, and, D. B. Moody. 2005. Mycobacterium tuberculosis regulates CD1 antigen presentation pathways through TLR-2. J. Immunol. 175:17581766.
39. Moody, D. B.,, D.C. Young,, T.-Y. Cheng,, J.-P. Rosat,, C. Roura-Mir,, P. B. O’Connor,, D. M. Zajonc,, A. Walz,, M. J. Miller,, S. B. Levery,, I. A. Wilson,, C. E. Costello, and, M. B. Brenner. 2004. T cell activation by lipopeptide antigens. Science 303:527531.
40. Flynn, J. L., and, J. Chan. 2001. Immunology of tuberculosis. Annu. Rev. Immunol. 19:93129.
41. Flynn, J. L. 2004. Immunology of tuberculosis and implications in vaccine development. Tuberculosis 84:93101.
42. Jullien, D.,, S. Stenger,, W. A. Ernst, and, R. L. Modlin. 1997. CD1 presentation of microbial non-peptide antigens to T cells. J. Clin. Investig. 99:20712074.
43. Porcelli, S. A., and, R. L. Modlin. 1999. The CD1 system: antigen-presenting molecules for T-cell recognition of lipids and glycolipids. Annu. Rev. Immunol. 17:297329.
44. Hayes, S. M., and, K. L. Knight. 2001. Group 1 CD1 genes in rabbit. J. Immunol. 166:403410.
45. Sköld, M., and, S. M. Behar. 2003. The role of CD1d-restricted NKT cells in microbial immunity. Infect. Immun. 71:54475455.
46. Dascher, C. C.,, K. Hiromatsu,, X. Xiong,, C. Morehouse,, G. Watts,, G. Liu,, D. N. McMurray,, K. P. LeClair,, S. A. Porcelli, and, M. B. Brenner. 2003. Immunization with a mycobacterial lipid vaccine improves pulmonary pathology in the guinea pig model of tuberculosis. Int. Immunol. 15:915925.
47. Granucci, F.,, S. Feau,, I. Zanoni,, N. Pavelka,, C. Vizzardelli,, G. Raimondi, and, P. Ricciardi-Castagnoli. 2003. The immune response is initiated by dendritic cells via interaction with microorganisms and interleukin-2 production. J. Infect. Dis. 187(Suppl. 2):S346S350.
48. Germain, R. N., and, M. K. Jenkins. 2004. In vivo antigen presentation. Curr. Opin. Immunol. 16:120125.
49. Majno, G., and, I. Joris. 2004. Cells, Tissues, and Disease: Principles of General Pathology, 2nd ed. Oxford University Press, New York, N.Y.
50. Schlesinger, L. S. 1996. Role of mononuclear phagocytes in M. tuberculosis pathogenesis. J. Investig. Med. 44:312323.
51. North, R. J., and, Y. J. Jung. 2004. Immunity to tuberculosis. Annu. Rev. Immunol. 22:599623.
52. Means, T. K.,, S. Wang,, E. Lien,, A. Yoshimura,, D. T. Golenbock, and, M. J. Fenton. 1999. Human toll-like receptors mediate cellular activation by Mycobacterium tuberculosis. J. Immunol. 163:39203927.
53. Krutzik, S. R., and, R. L. Modlin. 2004. The role of Toll-like receptors in combating mycobacteria. Semin. Immunol. 16:3541.
54. Brightbill, H. D.,, D. H. Libraty,, S. R. Krutzik,, R. B. Yang,, J. T. Belisle,, J. R. Bleharski,, M. Maitland,, M. V. Norgard,, S. E. Plevy,, S. T. Smale,, P. J. Brennan,, B. R. Bloom,, P. J. Godowski, and, R. L. Modlin. 1999. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285:732736.
55. Shim, T. S.,, O. C. Turner, and, I. M. Orme. 2003. Toll-like receptor 4 plays no role in susceptibility of mice to Mycobacterium tuberculosis infection. Tuberculosis (Edinb.) 83:367371.
56. Reiling, N.,, C. Holscher,, A. Fehrenbach,, S. Kroger,, C. J. Kirschning,, S. Goyert, and, S. Ehlers. 2002. Toll-like receptor-2 (TLR2)- and TLR4-mediated pathogen recognition in resistance to airborne infection with Mycobacterium tuberculosis. J. Immunol. 169:34803484.
57. Abel, B.,, N. Thieblemont,, V. J. Quesniaux,, N. Brown,, J. Mpagi,, K. Miyake,, F. Bihl, and, B. Ryffel. 2002. Toll-like receptor 4 expression is required to control chronic Mycobacterium tuberculosis infection in mice. J. Immunol. 169:31553162.
58. Armstrong, J. A., and, P. D. Hart. 1971. Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J. Exp. Med. 134:713740.
59. Russell, D. G. 2001. Mycobacterium tuberculosis: here today, and here tomorrow. Nat. Rev. Mol. Cell Biol. 2:569577.
60. Pieters, J. 2001. Entry and survival of pathogenic mycobacteria in macrophages. Microbes Infect. 3:249255.
61. Russell, D. G.,, H. C. Mwandumba, and, E. E. Rhoades. 2002. Mycobacterium and the coat of many lipids. J. Cell Biol. 158:421426.
62. Russell, D. G.,, G. E. Purdy,, R. M. Owens,, K. H. Rohde, and, R. M. Yates. 2005. Mycobacterium tuberculosis and the four-minute phagosome. ASM News 71:459463.
63. Walburger, A.,, A. Koul,, G. Ferrari,, L. Nguyen,, C. Prescianotto-Baschong,, K. Huygen,, B. Klebl,, C. Thompson,, G. Bacher, and, J. Pieters. 2004. Protein kinase G from pathogenic mycobacteria promotes survival within macrophages. Science 304:18001804.
64. Ting, L. M.,, A. C. Kim,, A. Cattamanchi, and, J. D. Ernst. 1999. Mycobacterium tuberculosis inhibits IFN-gamma transcriptional responses without inhibiting activation of STAT1. J. Immunol. 163:38983906.
65. McKinney, J. D.,, K. Höner zu Bentrup,, E. J. Muñoz-Elias,, A. Miczak,, B. Chen,, W. T. Chan,, D. Svenson,, J. C. Sacchettini,, W. R. Jacobs, Jr., and, D. G. Russell. 2000. Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature 406:735738.
66. Daniel, J.,, C. Deb,, V. S. Dubey,, T. D. Sirakova,, B. Abomoelak,, H. R. Morbidoni, and, P. E. Kolattukudy. 2004. Induction of a novel class of diacylglycerol acyltransferase and triglycerol accumulation in Mycobacterium tuberculosis as it goes into a dormancy-like state in culture. J. Bacteriol. 186:50175030.
67. Long, R.,, B. Light, and, J. A. Talbot. 1999. Mycobacteriocidal action of exogenous nitric oxide. Antimicrob. Agents Chemother. 43:403405.
68. MacMicking, J. D.,, R. J. North,, R. LaCourse,, J. S. Mudgett,, S. K. Shah, and, C. F. Nathan. 1997. Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc. Natl. Acad. Sci. USA 94:52435248.
69. Scanga, C. A.,, V. P. Mohan,, K. Tanaka,, D. Alland,, J. L. Flynn, and, J. Chan. 2001. The inducible nitric oxide synthase locus confers protection against aerogenic challenge of both clinical and laboratory strains of Mycobacterium tuberculosis in mice. Infect. Immun. 69:77117717.
70. Scanga, C. A.,, V. P. Mohan,, H. Joseph,, K. Yu,, J. Chan, and, J. L. Flynn. 1999. Reactivation of latent tuberculosis: variations on the Cornell murine model. Infect. Immun. 67:45314538.
71. Darwin, K. H.,, S. Ehrt,, J. C. Gutierrez-Ramos,, N. Weich, and, C. F. Nathan. 2003. The protea-some of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 302:19631966.
72. Pieters, J., and, H. Ploegh. 2003. Chemical warfare and mycobacterial defense. Science 302:19001902.
73. Rees, R. J. W., and, P. D. Hart. 1961. Analysis of the host-parasite equilibrium in chronic murine tuberculosis by total and viable bacillary counts. Br. J. Exp. Pathol. 42:8388.
74. Muñoz-Elías, E. J.,, J. Timm,, T. Botha,, W.-T. Chan,, J. E. Gomez, and, J. D. McKinney. 2005. Replication dynamics of Mycobacterium tuberculosis in chronically infected mice. Infect. Immun. 73:546551.
75. Shi, L.,, Y.-J. Jung,, S. Tyagi,, M. L. Gennaro, and, R. J. North. 2003. Expression of Th1-mediated immunity in mouse lungs induces a Mycobacterium tuberculosis transcription pattern characteristic of nonreplicating persistence. Proc. Natl. Acad. Sci. USA 100:241246.
76. Schnappinger, D.,, S. Ehrt,, M. I. Voskuil,, Y. Liu,, J. A. Mangan,, I. M. Monahan,, G. Dolganov,, B. Efron,, P. D. Butcher,, C. Nathan, and, G. K. Schoolnik. 2003. Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: insights into the phagosomal environment. J. Exp. Med. 198:693704.
77. Voskuil, M. I.,, D. Schnappinger,, K. C. Visconti,, M. I. Harrell,, G. M. Dolganov,, D. R. Sherman, and, G. K. Schoolnik. 2003. Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J. Exp. Med. 198:705713.
78. Higuchi, S.,, M. Suga,, A M. Dannenberg, Jr.,, L. F. Affronti,, I. Azuma,, T. M. Daniel, and, J. P. Petrali. 1981. Persistence of protein, carbohydrate and wax components of tubercle bacilli in dermal BCG lesions. Am. Rev. Respir. Dis. 123:397401.
79. Langewoort, H. L.,, Z. A. Cohn,, J. G. Hirsch,, J. H. Humphrey,, W. G. Spector, and, R. van Furth. 1970. The nomenclature of mononuclear phagocytic cells, p.16. In R. van Furth (ed.), Mononuclear Phagocytes. F. A. Davis Co., Philadelphia, Pa.
80. Dannenberg, A. M., Jr. 1968. Cellular hypersensitivity and cellular immunity in the pathogenesis of tuberculosis: specificity, systemic and local nature, and associated macrophage enzymes. Bacteriol. Rev. 32:85102.
81. Dannenberg, A. M., Jr.,, O. T. Meyer,, J. R. Esterly, and, T. Kambara. 1968. The local nature of immunity in tuberculosis, illustrated histochemically in dermal BCG lesions. J. Immunol. 100:931941.
82. Suga, M.,, A. M. Dannenberg, Jr., and, S. Higuchi. 1980. Macrophage functional heterogeneity in vivo: macrolocal and microlocal macrophage activation, identified by double-staining tissue sections of BCG granulomas for pairs of enzymes. Am. J. Pathol. 99:305324.
83. Mosser, D. M. 2003. The many faces of macrophage activation. J. Leukoc. Biol. 73:209212.
84. Dannenberg, A. M., Jr.,, M. S. Burstone,, P. C. Walter, and, J. W. Kinsley. 1963. A histochemical study of phagocytic and enzymatic functions of rabbit mononuclear and polymorphonuclear exu-date cells and alveolar macrophages. I. Survey and quantitation of enzymes, and states of cellular activation. J. Cell Biol. 17:465486.
85. Nathan, C., and, M. Sporn. 1991. Cytokines in context. J. Cell Biol. 113:981986.
86. Nathan, C. F. 1987. Secretory products of macrophages. J. Clin. Investig. 79:319326.
87. Nathan, C. 2002. Points of control in inflammation. Nature 420:846852.
88. Cohn, Z. A., and, B. Benson. 1965. The in vitro differentiation of mononuclear phagocytes. III. The reversibility of granule and hydrolytic enzyme formation and the turnover of granule constituents. J. Exp. Med. 122:455466.
89. Dannenberg, A. M., Jr.,, P. C. Walter, and, F. A. Kapral. 1963. A histochemical study of phagocytic and enzymatic functions of rabbit mononu-clear and polymorphonuclear exudate cells and alveolar macrophages. II. The effect of particle ingestion on enzyme activity; two phases of in vitro activation. J. Immunol. 90:448465.
90. Ando, M.,, A. M. Dannenberg, Jr.,, M. Sugimoto, and, B. S. Tepper. 1977. Histochemical studies relating the activation of macrophages to the intracellular destruction of tubercle bacilli. Am. J. Pathol. 86:623634.
91. Dannenberg, A. M., Jr., and, E. L. Smith. 1955. Proteolytic enzymes of lung. J. Biol. Chem. 215:4554.
92. Dannenberg, A. M., Jr., and, E. L. Smith. 1955. Action of proteinase I of bovine lung. Hydrolysis of the oxidized B chain of insulin; polymer formation from amino acid esters. J. Biol. Chem. 215:5566.
93. Dannenberg, A. M., Jr., and, W. E. Bennett. 1964. Hydrolytic enzymes of rabbit mononuclear exudate cells. I. Quantitative assay and properties of certain proteases, nonspecific esterases and lipases of mononuclear and polymorphonuclear cells and erythrocytes. J. Cell Biol. 21:113.
94. Dannenberg, A. M., Jr., and, W. E. Bennett. 1963. Hydrolases of mononuclear exudate cells and tuberculosis. I. Exudate characteristics, esterases, proteinases and lipase. Arch. Pathol. 76:581591.
95. Yarborough, D. J.,, O. T. Meyer,, A. M. Dannenberg, Jr., and, B. Pearson. 1967. Histo-chemistry of macrophage hydrolases. III. Studies on β-galactosidase, β-glucuronidase and aminopeptidase with indolyl and naphthyl substrates. J. Reticuloendothel. Soc. 4:390408.
96. Mizunoe, K., and, A. M. Dannenberg, Jr. 1965. Hydrolases of rabbit macrophages. III. Effect of BCG vaccination, tissue culture, and ingested tuber-cle bacilli. Proc. Soc. Exp. Biol. Med. 120:284290.
97. Carson, M. E., and, A. M. Dannenberg, Jr. 1965. Hydrolytic enzymes of rabbit mononuclear exudate cells. II. Lysozyme: properties and quantitative assay in tuberculous and control inbred rabbits. J. Immunol. 94:99104.
98. Meyer, O. T.,, A. M. Dannenberg, Jr., and, K. Mizunoe. 1970. Hydrolytic enzymes of rabbit mononuclear and polymorphonuclear exudate cells and pulmonary alveolar macrophages. III. Deoxyribonuclease and ribonuclease: properties and quantitative assay in macrophages from tuberculous and control inbred rabbits. J. Reticuloendothel. Soc. 7:1531.
99. Rojas-Espinosa, O.,, A. M. Dannenberg, Jr.,, P. A. Murphy,, P. A. Straat,, P. C. Huang, and, S. P. James. 1973. Purification and properties of the cathepsin D-type proteinase from beef and rabbit lung and its identification in macrophages. Infect. Immun. 8:10001008.
100. Rojas-Espinosa, O.,, P. Arce-Paredez,, A. M. Dannenberg, Jr., and, R. L. Kamenetz. 1975. Macrophage esterase: identification, purification and properties of a chymotrypsin-like esterase from lung that hydrolyzes and transfers nonpolar amino acid esters. Biochim. Biophys. Acta 403:161179.
101. McAdoo, M. H.,, A. M. Dannenberg, Jr.,, C. J. Hayes,, S. P. James, and, J. H. Sanner. 1973. Inhibition of the cathepsin D-type proteinase of macrophages by pepstatin, a specific pepsin inhibitor, and other substances. Infect. Immun. 7:655665.
102. Hastie, A. T. 1981. Monospecific antibodies to rabbit lung ribonucleases. J. Biol. Chem. 256:1255312560.
103. Namba, M.,, M. Suga,, F. Tanaka,, A. M. Dannenberg, Jr.,, A. T. Hastie, and, R. C. Franson. 1983. Immunocytochemical demonstration of rabbit ribonuclease and phospholipase A2 by the peroxidase-antiperoxidase technique in professional phagocytes (pulmonary alveolar macrophages and granulocytic and mononuclear peritoneal exudate cells) and in glycol methacrylate sections of dermal tuberculous (BCG) lesions. J. Reticuloendothel. Soc. 34:425435.
104. Rojas-Espinosa, O.,, A. M. Dannenberg, Jr.,, L. A. Sternberger, and, T. Tsuda. 1974. Role of cathepsin D in the pathogenesis of tuberculosis. A histochemical study employing unlabeled antibodies and the peroxidase-antiperoxidase complex. Am. J. Pathol. 74:117.
105. Tsuda, T.,, A. M. Dannenberg, Jr.,, M. Ando,, O. Rojas-Espinosa, and, K. Shima. 1974. Enzymes in tuberculous lesions hydrolyzing pro-tein, hyaluronic acid and chondroitin sulfate: a study of isolated macrophages in developing and healing rabbit BCG lesions with substrate film techniques; the shift of enzyme pH optima towards neutrality in “intact” cells and tissues. J. Reticuloendothel. Soc. 16:220231.
106. Smokovitis, A.,, M. Sugimoto,, A. M. Dannenberg, Jr., and, T. Astrup. 1976. A histo-chemical study of the fibrinolytic activity in dermal tuberculous lesions produced by BCG in rabbits. Exp. Mol. Pathol. 25:236241.
107. Rivera-Marrero, C. A.,, J. Stewart,, W. M. Shafer, and, J. Roman. 2004. Down-regulation of cathepsin G in THP-1 monocytes after infection with Mycobacterium tuberculosis is associated with increased intracellular survival of bacilli. Infect. Immun. 72:57125721.
108. Sugimoto, M.,, A. M. Dannenberg, Jr.,, L. M. Wahl,, W. H. Ettinger, Jr.,, A. T. Hastie,, D.C. Daniels,, C. R. Thomas, and, L. Demoulin-Brahy. 1978. Extracellular hydrolytic enzymes of rabbit dermal tuberculous lesions and tuberculin reactions collected in skin chambers. Am. J. Pathol. 90:583608.
109. Sheldon, W. H.,, D. Mildvan, and, J. C. Allen. 1967. Some serum protein and cellular constituents of inflammatory lesions. Collection of exudates in a chamber adhered over skin wounds of rabbits. Johns Hopkins Med. J. 121:113133.
110. Edlow, D. W., and, W. H. Sheldon. 1971. The pH of inflammatory exudates. Proc. Soc. Exp. Biol. Med. 137:13281332.
111. Lurie, M. B. 1932. The correlation between the histological changes and the fate of living tuber-cle bacilli in the organs of tuberculous rabbits. J. Exp. Med. 55:3154.
112. Lurie, M. B. 1964. Resistance to Tuberculosis: Experimental Studies in Native and Acquired Defensive Mechanisms. Harvard University Press, Cambridge, Mass.
113. Dannenberg, A. M., Jr. 2003. Macrophage turnover, division and activation within developing, peak and “healed” tuberculous lesions produced in rabbits by BCG. Tuberculosis 83:251260.
114. Mustafa, T.,, S. Phyu,, R. Nilsen,, R. Jonsson, and, G. Bjune. 2000. In situ expression of cytokines and cellular phenotypes in the lungs of mice with slowly progressive primary tuberculosis. Scand. J. Immunol. 51:548556.
115. Orme, I. M. 1993. Immunity to mycobacteria. Curr. Opin. Immunol. 5:497502.
116. Khaled, A. R., and, S. K. Durum. 2002. Lymphocide: cytokines and the control of lymphoid homeostasis. Nat. Rev. Immunol. 2:817830.
117. Marleau, A. M., and, N. Sarvetnick. 2005. T cell homeostasis in tolerance and immunity. J. Leukoc. Biol. 78:575584.
118. Trinchieri, G. 1997. Cytokines acting on or secreted by macrophages during intracellular infection (IL-10, IL-12, IFN-γ). Curr. Opin. Immunol. 9:1723.
119. Shigenaga, T.,, A. M. Dannenberg, Jr.,, D. B. Lowrie,, W. Said,, M. J. Urist,, H. Abbey,, B. H. Schofield,, P. Mounts, and, K. Sugisaki. 2001. Immune responses in tuberculosis: antibodies and CD4/CD8 lymphocytes with vascular adhesion molecules and cytokines (chemokines) cause a rapid antigen-specific cell infiltration at sites of bacillus Calmette-Guérin reinfection. Immunology 102:466479.
120. Lewinsohn, D. A.,, A. S. Heinzel,, J. M. Gardner,, L. Zhu,, M. R. Alderson, and, D. M. Lewinsohn. 2003. Mycobacterium tuberculosis- specific CD8+ T cells preferentially recognize heavily infected cells. Am. J. Respir. Crit. Care Med. 168:13461352.
121. Harty, J. T.,, A. R. Tvinnereim, and, D. W. White. 2000. CD8+ T cell effector mechanisms in resistance to infection. Annu. Rev. Immunol. 18:275308.
122. Janeway, C. A., Jr. 2002. A trip through my life with an immunological theme. Annu. Rev. Immunol. 20:128.
123. Wakkach, A.,, N. Fournier,, V. Brun,, J.-P. Breittmayer,, F. Cottrez, and, H. Groux. 2003. Characterization of dendritic cells that induce tolerance and T-regulatory-1 cell differentiation in vivo. Immunity 18:605617.
124. von Boehmer, H. 2003. Dynamics of suppressor T cells: in vivo veritas. J. Exp. Med. 198:845849.
125. Levy, B. D.,, C. B. Clish,, B. Schmidt,, K. Gronert, and, C. N. Serhan. 2001. Lipid mediator class switching during acute inflammation: signals in resolution. Nat. Immunol. 2:612619.
126. Walker, L. S. K. 2003. CD4+ CD25+ Treg: divide and rule? Immunology 111:129137.
127. Akbar, A. N.,, L. S. Taams,, M. Salmon, and, M. Vukmanovic-Stejic. 2003. The peripheral generation of CD4+ CD25+ regulatory T cells. Immunology 109:319325.
128. Rubin, B.,, Y. D. de Durana,, N. Li, and, E. E. Sercarz. 2003. Regulator T cells: specific for antigen and/or antigen receptors? Scand. J. Immunol. 57:399409.
129. Baecher-Allan, C.,, V. Viglietta, and, D. A. Hafler. 2004. Human CD4+CD25+ regulatory T cells. Semin. Immunol. 16:8997.
130. Horwitz, D. A.,, S. G. Zheng, and, J. D. Gray. 2003. The role of the combination of IL-2 and TGF-β or IL-10 in the generation and function of CD4+CD25+ and CD8+ regulatory T cell subsets. J. Leukoc. Biol. 74:471478.
131. Piccirillo, A. C., and, E. M. Shevach. 2004. Naturally-occurring CD4+CD25+ immunoreg-ulatory T cells: central players in the arena of peripheral tolerance. Semin. Immunol. 16:8188.
132. Shevach, E. M. 2004. Regulatory/suppressor T cells in health and disease. Arthritis Rheum. 50:27212724.
133. Belkaid, Y., and, B. T. Rouse. 2005. Natural regulatory T cells in infectious disease. Nat. Immunol. 6:353360.
134. Hayday, A. C. 2000. γδ cells: a right time and a right place for a conserved third way of protection. Annu. Rev. Immunol. 18:9751026.
135. Ladel, C. H.,, C. Blum,, A. Dreher,, K. Reifenberg, and, S. H. Kaufmann. 1995. Protective role of gamma/delta T cells and alpha/beta T cells in tuberculosis. Eur. J. Immunol. 25:28772881.
136. D’souza, C. D.,, A. M. Cooper,, A. A. Frank,, R. J. Mazzaccaro,, B. R. Bloom, and, I. M. Orme. 1997. An anti-inflammatory role for gamma delta T lymphocytes in acquired immunity to Mycobacterium tuberculosis. J. Immunol. 158:12171221.
137. Balbi, B.,, M. T. Valle,, S. Oddera,, D. Giunti,, F. Manca,, G. A. Rossi, and, L. Allegra. 1993. T-lymphocytes with gamma delta+ V delta 2+ antigen receptors are present in increased proportions in a fraction of patients with tuberculosis or with sarcoidosis. Am. Rev. Respir. Dis. 148:16851690.
138. Chen, Z. W., and, N. L. Letvin. 2003. Vgamma2Vdelta2+ T cells and anti-microbial immune responses. Microbes Infect. 5:491498.
139. Ito, M.,, N. Kojiro,, T. Ikeda,, T. Ito,, J. Funada, and, T. Kokubu. 1992. Increased proportions of peripheral blood gamma-delta T cells in patients with pulmonary tuberculosis. Chest 102:195197.
140. Ueta, C.,, I. Tsuyuguchi,, H. Kawasumi,, T. Takashima,, H. Toba, and, S. Kishimoto. 1994. Increase of gamma/delta T cells in hospital workers who are in close contact with tuberculosis patients. Infect. Immun. 62:54345441.
141. Li, B.,, M. D. Rossman,, T. Imir,, A. F. Oner-Eyuboglu,, C. W. Lee,, R. Biancaniello, and, S. R. Carding. 1996. Disease-specific changes in gamma-delta T cell repertoire and function in patients with pulmonary tuberculosis. J. Immunol. 157:42224229.
142. Carvalho, A. C.,, A. Matteelli,, P. Airo,, S. Tedoldi,, C. Casalini,, L. Imberti,, G. P. Cadeo,, A. Beltrame, and, G. Carosi. 2002. Gamma-delta T lymphocytes in the peripheral blood of patients with tuberculosis with and without HIV co-infection. Thorax 57:357360.
143. Gioia, C.,, C. Agrati,, R. Casetti,, C. Cairo,, G. Borsellino,, L. Battistini,, G. Mancino,, D. Goletti,, V. Colizzi,, L. P. Pucillo, and, F. Poccia. 2002. Lack of CD27-CD45RA-V gamma 9V delta 2+ T cell effectors in immunocompromised hosts and during active pulmonary tuberculosis. J. Immunol. 168:14841489.
144. Boismenu, R., and, W. L. Havran. 1997. An innate view of γδ T cells. Curr. Opin. Immunol. 9:5763.
145. Kaufmann, S. H. E. 2003. Immunity to intra-cellular bacteria, p. 12291261. In W. E. Paul (ed.), Fundamental Immunology. Lippincott Williams & Wilkins, Philadelphia, Pa.
146. Shen, Y.,, D. Zhou,, L. Qiu,, X. Lai,, M. Simon,, L. Shen,, Z. Kou,, Q. Wang,, L. Jiang,, J. Estep,, R. Hunt,, M. Clagett,, P. K. Sehgal,, Y. Li,, X. Zeng,, C. T. Morita,, M. B. Brenner,, N. L. Letvin, and, Z. W. Chen. 2002. Adaptive immune response of Vgamma2Vdelta2+ T cells during mycobacterial infections. Science 295:22552258.
147. Hahn, Y.-S.,, C. Taube,, N. Jin,, K. Takeda,, J.-W. Park,, J. M. Wands,, M. K. Aydintug,, C. L. Roark,, M. Lahn,, R. L. O’Brien,, E. W. Gelfand, and, W. K. Born. 2003. Vγ4+ γδ T cells regulate airway hyperreactivity to methacholine in ovalbumin-sensitized and challenged mice. J. Immunol. 171:31703178.
148. Robbins, S. H., and, L. Brossay. 2002. NK cell receptors: emerging roles in host defense against infectious agents. Microbes Infect. 4:15231530.
149. Raulet, D. H. 2003. Natural killer cells, p.365391. In W. E. Paul (ed.), Fundamental Immunology. Lippincott Williams & Wilkins, Philadelphia, Pa.
150. Atochina, O., and, D. Harn. 2005. LNFPIII/LeX-stimulated macrophages activate natural killer cells via CD40-CD40L interaction. Clin. Diagn. Lab. Immunol. 12:10411049.
151. Kronenberg, M., and, L. Gapin. 2002. The unconventional lifestyle of NKT cells. Nat. Rev. Immunol. 2:557568.
152. Yoneda, T., and, J. J. Ellner. 1998. CD4(+) T cell and natural killer cell-dependent killing of Myco-bacterium tuberculosis by human monocytes. Am. J. Respir. Crit. Care Med. 158:395403.
153. Bermudez, L. E.,, M. Wu, and, L. S. Young. 1995. Interleukin-12-stimulated natural killer cells can activate human macrophages to inhibit growth of Mycobacterium avium. Infect. Immun. 63:40994104.
154. Lieberman, L. A., and, C. A. Hunter. 2002. Regulatory pathways involved in the infection-induced production of IFN-γ by NK cells. Microbes Infect. 4:15311538.
155. Junqueira-Kipnis, A. P.,, A. Kipnis,, A. Jamieson,, M. Gonzales Juarrero,, A. Diefen-bach,, D. H. Raulet,, J. Turner, and, I. M. Orme. 2003. NK cells respond to pulmonary infection with Mycobacterium tuberculosis, but play a minimal role in protection. J. Immunol. 171:60396045.
156. Orange, J. S. 2002. Human natural killer cell deficiencies and susceptibility to infection. Microbes Infect. 4:15451558.
157. Andrews, D. M.,, A. A. Scalzo,, W. M. Yokoyama,, M. J. Smyth, and, M. A. Degli-Esposti. 2003. Functional interactions between dendritic cells and NK cells during vital infection. Nat. Immunol. 4:175181.
158. Moretta, A. 2002. Natural killer cells and dendritic cells: rendezvous in abused tissues. Nat. Rev. Immunol. 2:957964.
159. Barry, M., and, R. C. Bleackley. 2002. Cytotoxic T lymphocytes: all roads lead to death. Nat. Rev. Immunol. 2:401409.
160. Rock, K. L. 2003. The ins and outs of cross-presentation. Nat. Immunol. 4:941943.
161. van Parijs, L., and, A. K. Abbas. 1996. Role of Fas-mediated cell death in the regulation of immune responses. Curr. Opin. Immunol. 8:355361.
162. Mangan, D. F., and, S. M. Wahl. 1991. Differential regulation of human monocyte programmed cell death (apoptosis) by chemotactic factors and pro-inflammatory cytokines. J. Immunol. 147:34083412.
163. Sugisaki, K.,, A. M. Dannenberg, Jr.,, Y. Abe,, J. Tsuruta,, W.-J. Su,, W. Said,, L. Feng,, T. Yoshimura,, P. J. Converse, and, P. Mounts. 1998. Nonspecific and immune-specific up-regulation of cytokines in rabbit dermal tuberculous (BCG) lesions. J. Leukoc. Biol. 63:440450.
164. Vogt, R. F., Jr.,, N. A. Hynes,, A. M. Dannenberg, Jr.,, S. Castracane, and, L. Weiss. 1983. Improved techniques using Giemsa-stained glycol methacrylate tissue sections to quantitate basophils and other leukocytes in inflammatory skin lesions. Stain Technol. 58:193205.
165. Bennouna, S.,, S. K. Bliss,, T. J. Curiel, and, E. Y. Denkers. 2003. Cross-talk in the innate system: neutrophils instruct recruitment and activation of dendritic cells during microbial infection. J. Immunol. 171:60526058.
166. Brandt, E.,, F. Petersen,, A. Ludwig,, J. E. Ehlert,, L. Bock, and, H.-D. Flad. 2000. The β-thromboglobulins and platelet factor 4: blood platelet-derived CXC chemokines with divergent roles in early neutrophil regulation. J. Leukoc. Biol. 67:471478.
167. Simon, H.-U. 2003. Neutrophil apoptosis pathways and their modifications in inflammation. Immunol. Rev. 193:101110.
168. Lasco, T. M.,, O. C. Turner,, L. Cassone,, I. Sugawara,, H. Yamada,, D. N. McMurray, and, I. M. Orme. 2004. Rapid accumulation of eosinophils in lung lesions in guinea pigs infected with Mycobacterium tuberculosis. Infect. Immun. 72:11471149.
169. Munitz, A., and, F. Levi-Schaffer. 2004. Eosinophils: ‘new’ roles for ‘old’ cells. Allergy 59:268275.
170. Ruth, J. H.,, N. W. Lukacs,, K. S. Warmington,, T. J. Polak,, M. Burdick,, S. L. Kunkel,, R. M. Strieter, and, S. W. Chensue. 1998. Expression and participation of eotaxin during microbacterial (Type 1) and schistosomal (Type 2) antigen-elicited granuloma formation. J. Immunol. 161:42764282.
171. Vogt, R. F., Jr.,, A. M. Dannenberg, Jr.,, B. H. Schofield,, N. A. Hynes, and, B. Papirmeister. 1984. Pathogenesis of skin lesions caused by sulfur mustard. Fundam. Appl. Toxicol. 4:S71S83.
172. Dannenberg, A. M., Jr.,, P. J. Pula,, L. Liu,, S. Harada,, F. Tanaka,, R. F. Vogt, Jr.,, A. Kajiki, and, K. Higuchi. 1985. Inflammatory mediators and modulators released in organ culture from rabbit skin lesions produced in vivo by sulfur mustard. I. Quantitative histopathology; PMN, basophil and mononuclear cell survival; and unbound (serum) protein content. Am. J. Pathol. 121:1527.
173. Rikimaru, T.,, M. Nakamura,, T. Yano,, G. Beck,, G. S. Habicht,, L. L. Rennie,, M. Widra,, C. A. Hirshman,, M. G. Boulay,, E. W. Spannhake,, G. S. Lazarus,, P. J. Pula, and, A. M. Dannenberg, Jr. 1991. Mediators, initiating the inflammatory response, released in organ culture by full-thickness human-skin explants exposed to the irritant, sulfur mustard. J. Investig. Dermatol. 96:888897.
174. Namba, M.,, A. M. Dannenberg, Jr., and, F. Tanaka. 1983. Improvement of the histo-chemical demonstration of acid phosphatase, β-galactosidase and nonspecific esterase in glycol methacrylate tissue sections by cold temperature embedding. Stain Technol. 58:207213.
175. Higuchi, S.,, M. Suga,, A. M. Dannenberg, Jr., and, B. H. Schofield. 1979. Histochemical demonstration of enzyme activities in plastic- and paraffin-embedded tissue sections. Stain Technol. 54:512.
176. Galli, S. J., and, S. Nakae. 2003. Mast cells to the defense. Nat. Immunol. 4:11601162.
177. McLachlan, J. B.,, J. P. Hart,, S. V. Pizzo,, C. P. Shelburne,, H. F. Staats,, M. D. Gunn, and, S. N. Abraham. 2003. Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection. Nat. Immunol. 4:11991205.
178. Dvorak, A. M. 2005. Ultrastructural studies of human basophils and mast cells. J. Histochem. Cytochem. 53:10431070.
179. Kajiki, A.,, K. Higuchi,, M. Nakamura,, L. H. Liu,, P. J. Pula, and, A. M. Dannenberg, Jr. 1988. Sources of extracellular lysosomal enzymes released in organ culture by developing and healing inflammatory lesions. J. Leukoc. Biol. 43:104116.
180. Harada, S.,, A. M. Dannenberg, Jr.,, A. Kajiki,, K. Higuchi,, F. Tanaka, and, P. J. Pula. 1985. Inflammatory mediators and modulators released in organ culture from rabbit skin lesions produced in vivo by sulfur mustard. II. Evans blue dye experiments that determined the rates of entry and turnover of serum protein in developing and healing lesions. Am. J. Pathol. 121:2838.
181. Moqbel, R., and, P. Lacy. 1998. Eosinophils, p. 139165. In J. A. Denburg (ed.), Allergy and Allergic Diseases: the New Mechanisms and Therapeutics. Humana Press, Totowa, N. J.
182. Gleich, G. J.,, C. R. Adolphson, and, K. M. Leiferman. 1992. Eosinophils, p. 663700. In J. I. Gallin,, I. M. Goldstein, and, R. Snyderman (ed.), Inflammation: Basic Principles and Clinical Correlates, 2nd ed. Raven Press, Ltd., New York, N.Y.

Tables

Generic image for table
TABLE 1

Major cell types involved in specific and nonspecific host defense reactions against the tubercle bacillus a

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
Generic image for table
TABLE 2

β-Galactosidase (β-Gal) activity and the number of acid-fast bacilli seen in immature and mature epithelioid cells in nonnecrotic granulation tissue of dermal BCG lesions a

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
Generic image for table
TABLE 3

Macrophage activation and 14C-labeled bacillary components within dermal BCG lesions

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6
Generic image for table
TABLE 4

Percentage of CD4 and CD8 lymphocytes in the mononuclear cell population of primary BCG lesions during their development and healing a

Citation: Dannenberg, Jr. A. 2006. Macrophages and Other Cells in Tuberculous Lesions, p 120-152. In Pathogenesis of Human Pulmonary Tuberculosis. ASM Press, Washington, DC. doi: 10.1128/9781555815684.ch6

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