Chapter 6 : Phagocytes and Anti-Infective Immunity

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This chapter presents an overview of the role played by phagocytes in anti-infective immunity. It describes the various types and functions of phagocytic cells, the mechanisms they utilize for microbial recognition, uptake, and killing; and their involvement with the adaptive immune system. Where appropriate, the authors demonstrate how pathogens have overcome the various anti-infective phagocyte functions and indicate where these microbial mechanisms have aided the understanding of phagocyte cell biology. Phagocytes can contribute to the generation of autoimmune diseases by presenting microbial epitopes to lymphocytes which are cross-reactive to self molecules. The respiratory burst of phagocytes that culminates in the production of reactive oxygen intermediates is one of the best characterized antimicrobial defenses. A central role of phagocytes, particularly dendritic cells (DC), in the generation of adaptive immunity is that of antigen presentation. Phagocytes play a central role in anti-infective immunity, which is important in all aspects of the immune response.

Citation: Brown G, Gordon S. 2002. Phagocytes and Anti-Infective Immunity, p 79-92. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch6
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Figure 1

Properties and ligands of selected PRRs. Abbreviations: LBP, LPS-binding protein; LTA, lipoteichoic acid; LDL, low-density lipoprotein; ICAM-1, intercellular cell adhesion molecule 1. The structures of the various receptors are reprinted, with permission, from 2nd edition ( ).

Citation: Brown G, Gordon S. 2002. Phagocytes and Anti-Infective Immunity, p 79-92. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch6
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Figure 2

FcγR and their isoforms. Shown are the tyrosine residues present in the ITAM (striped box) or ITIM (shaded box), which become phosphorylated after receptor cross-linking. The ITAM and ITIM sequences are also indicated.

Citation: Brown G, Gordon S. 2002. Phagocytes and Anti-Infective Immunity, p 79-92. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch6
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Figure 3

Schematic representation of phagocytosis and phagosomal maturation. Also shown are the strategies used by microbes to evade or modulate these processes.

Citation: Brown G, Gordon S. 2002. Phagocytes and Anti-Infective Immunity, p 79-92. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch6
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Figure 4

Schematic representation of the antigen-processing and antigen presentation pathways for MHC class I, MHC class II, and CD1 molecules. Dashed arrows indicate putative and/or unknown pathways.

Citation: Brown G, Gordon S. 2002. Phagocytes and Anti-Infective Immunity, p 79-92. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch6
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1. Aderem, A.,, and D. M. Underhill. 1999. Mechanisms of phagocytosis in macrophages. Annu. Rev. Immunol. 17: 593 623.
2. Armstrong, J.,, and P. Hart. 1971. Response of cultured macrophages to Mycobacterium tuberculosis with observations on fusion of lysosomes with phagosomes. J. Exp. Med. 134: 713 740.
3. Banchereau, J.,, and R. M. Steinman. 1998. Dendritic cells and the control of immunity. Nature 392: 245 252.
4. Barclay, A. N.,, M. H. Brown,, S. K. A. Law,, A. J. McKnight,, M. G. Tomlinson,, and P. A. van der Merwe. 1997. The Leucocyte Antigen FactsBook, 2nd ed. Academic Press, Inc., San Diego, Calif.
5. Beauregard, K. E.,, K. D. Lee,, R. J. Collier,, and J. A. Swanson. 1997. pH-dependent perforation of macrophage phagosomes by listeriolysin O from Listeria monocytogenes. J. Exp. Med. 186: 1159 1163.
6. Bell, D.,, J. W. Young,, and J. Banchereau. 1999. Dendritic cells. Adv. Immunol. 72: 255 324.
7. Berón, W.,, C. Alvarez-Dominguez,, L. Mayorga,, and P. D. Stahl. 1995. Membrane trafficking along the phagocytic pathway. Trends Cell Biol. 5: 100 104.
8. Billiau, A.,, H. Heremans,, K. Vermeire,, and P. Matthys. 1998. Immunomodulatory properties of interferon-gamma. An update. Ann. N. Y. Acad. Sci. 856: 22 32.
9. Biron, C. A. 1998. Role of early cytokines, including alpha and beta interferons (IFN-alpha / beta), in innate and adaptive immune responses to viral infections. Semin. Immunol. 10: 383 390.
10. Blackwell, J. M.,, and S. Searle. 1999. Genetic regulation of macrophage activation: understanding the function of Nramp1 (=Ity /Lsh/ Bcg). Immunol. Lett. 65: 73 80.
11. Burgner, D.,, K. Rockett,, and D. Kwiatkowski. 1999. Nitric oxide and infectious diseases. Arch. Dis. Child. 81: 185 188.
12. Busch, D. H.,, K. Kerksiek,, and E. G. Pamer. 1999. Processing of Listeria monocytogenes antigens and the in vivo T-cell response to bacterial infection. Immunol. Rev. 172: 163 169.
13. Canonne-Hergaux, F.,, S. Gruenheid,, G. Govoni,, and P. Gros. 1999. The Nramp1 protein and its role in resistance to infection and macrophage function. Proc. Assoc. Am. Physicians 111: 283 289.
14. Chang, K. P.,, and D. M. Dwyer. 1976. Multiplication of a human parasite (Leishmania donovani) in phagolysosomes of hamster macrophages in vitro. Science 193: 678 680.
15. Clark, R. A. 1999. Activation of the neutrophil respiratory burst oxidase. J. Infect. Dis. 179( Suppl. 2): S309 S317.
16. Cornelis, G. R. 1998. The Yersinia deadly kiss. J. Bacteriol. 180: 5495 5504.
17. Cossart, P.,, P. Boquet,, S. Normark,, and R. Rappuoli(ed.). 2000. Cellular Microbiology. ASM Press, Washington, D.C.
18. Cossart, P.,, and M. Lecuit. 1998. Interactions of Listeria monocytogenes with mammalian cells during entry and actin-based movement: bacterial factors, cellular ligands and signaling. EMBO J. 17: 3797 3806.
19. Cox, D.,, D. J. Lee,, B. M. Dale,, J. Calafat,, and S. Greenberg. 2000. A Rab11-containing rapidly recycling compartment in macrophages that promotes phagocytosis. Proc. Natl. Acad. Sci. USA 97: 680 685.
20. Cresswell, P. 1994. Assembly, transport, and function of MHC class II molecules. Annu. Rev. Immunol. 12: 259 293.
21. Descoteaux, A.,, and S. J. Turco. 1999. Glycoconjugates in Leishmania infectivity. Biochim. Biophys. Acta 1455: 341 352.
22. Desjardins, M.,, L. A. Huber,, R. G. Parton,, and G. Griffiths. 1994. Biogenesis of phagolysosomes proceeds through a sequential series of interactions with the endocytic apparatus. J. Cell Biol. 124: 677 688.
23. De Voss, J. J.,, K. Rutter,, B. G. Schroeder,, and C. E. Barry III. 1999. Iron acquisition and metabolism by mycobacteria. J. Bacteriol. 181: 4443 4451.
24. Ehlers, M. R.,, and M. Daffe. 1998. Interactions between Mycobacterium tuberculosis and host cells: are mycobacterial sugars the key? Trends Microbiol. 6: 328 335.
25. Fallman, M.,, K. Andersson,, S. Hakansson,, K. E. Magnusson,, O. Stendahl,, and H. Wolf-Watz. 1995. Yersinia pseudotuberculosis inhibits Fc receptor-mediated phagocytosis in J774 cells. Infect. Immun. 63: 3117 3124.
26. Fearon, D. T.,, and R. M. Locksley. 1996. The instructive role of innate immunity in the acquired immune response. Science 272: 50 53.
27. Fenton, M. J.,, and D. T. Golenbock. 1998. LPS-binding proteins and receptors. J. Leukoc. Biol. 64: 25 32.
28. Finlay, B. B.,, and S. Falkow. 1997. Common themes in microbial pathogenicity revisited. Microbiol. Mol. Biol. Rev. 61: 136 169.
29. Fitzpatrick, D. R.,, and H. Bielefeldt-Ohmann. 1999. Transforming growth factor beta in infectious disease: always there for the host and the pathogen. Trends Microbiol. 7: 232 236.
30. Fratazzi, C.,, R. D. Arbeit,, C. Carini,, M. K. Balcewicz-Sablinska,, J. Keane,, H. Kornfeld,, and H. G. Remold. 1999. Macrophage apoptosis in mycobacterial infections. J. Leukoc. Biol. 66: 763 764.
31. Gallin, J. I.,, R. Snyderman,, D. T. Fearon,, B. F. Haynes,, and C. Nathan (ed.). 1999. Inflammation: Basic Principles and Clinical Correlates, 3rd ed. Lippincott Williams & Wilkins, Philadelphia, Pa.
32. Goosney, D. L.,, D. G. Knoechel,, and B. B. Finlay. 1999. Enteropathogenic E. coli, Salmonella, and Shigella: masters of host cell cytoskeletal exploitation. Emerg. Infect. Dis. 5: 216 223.
33. Gordon, S., 1999a. Macrophages and the immune response, p. 533 545. In W. E. Paul (ed.), Fundamental Immunology, 4th ed. Lippincott-Raven Publishers, Philadelphia, Pa.
34. Gordon, S. (ed.). 1999b. Phagocytosis: Microbial Invasion, vol. 6. JAI Press Inc., Stamford, Conn.
35. Gordon, S. (ed.). 1999c. Phagocytosis: the Host, vol. 5. JAI Press Inc., Stamford, Conn.
36. Gresham, B. H.,, B. M. Dale,, J. W. Potter,, P. W. Chang,, C. M. Vines,, C. A. Lowell,, C. F. Lagenaur,, and C. L. Willman. 2000. Negative regulation of phagocytosis in murine macrophages by the Src kinase family member, Fgr. J. Exp. Med. 191: 515 528.
37. Griffin, F. M., Jr.,, J. A. Griffin,, J. E. Leider,, and S. C. Silverstein. 1975. Studies on the mechanism of phagocytosis. I. Requirements for circumferential attachment of particle-bound ligands to specific receptors on the macrophage plasma membrane. J. Exp. Med. 142: 1263 1282.
38. Griffin, F. M., Jr.,, J. A. Griffin,, and S. C. Silverstein. 1976. Studies on the mechanism of phagocytosis. II. The interaction of macrophages with anti-immunoglobulin IgG-coated bone marrowderived lymphocytes. J. Exp. Med. 144: 788 809.
39. Gruenheid, S.,, E. Pinner,, M. Desjardins,, and P. Gros. 1997. Natural resistance to infection with intracellular pathogens: the Nramp1 protein is recruited to the membrane of the phagosome. J. Exp. Med. 185: 717 730.
40. Hampton, M. B.,, A. J. Kettle,, and C. C. Winterbourn. 1998. Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood 92: 3007 3017.
41. Heinzen, R. A.,, M. A. Scidmore,, D. D. Rockey,, and T. Hackstadt. 1996. Differential interaction with endocytic and exocytic pathways distinguish parasitophorous vacuoles of Coxiella burnetii and Chlamydia trachomatis. Infect. Immun. 64: 796 809.
42. Herman, A.,, J. W. Kappler,, P. Marrack,, and A. M. Pullen. 1991. Superantigens: mechanism of T-cell stimulation and role in immune responses. Annu. Rev. Immunol. 9: 745 772.
43. High, N.,, J. Mounier,, M. C. Prevost,, and P. J. Sansonetti. 1992. IpaB of Shigella flexneri causes entry into epithelial cells and escape from the phagocytic vacuole. EMBO J. 11: 1991 1999.
44. Horwitz, M. A. 1983. Formation of a novel phagosome by the Legionnaires’ disease bacterium ( Legionella pneumophila) in human monocytes. J. Exp. Med. 158: 1319 1331.
45. Horwitz, M. A. 1984. Phagocytosis of the Legionnaires’ disease bacterium ( Legionella pneumophila) occurs by a novel mechanism: engulfment within a pseudopod coil. Cell 36: 27 33.
46. Inzana, T. J.,, J. Ma,, T. Workman,, R. P. Gogolewski,, and P. Anderson. 1988. Virulence properties and protective efficacy of the capsular polymer of Haemophilus ( Actinobacillus) pleuropneumoniae serotype 5. Infect. Immun. 56: 1880 1889.
47. Jones, T. C.,, and J. G. Hirsch. 1972. The interaction between Toxoplasma gondii and mammalian cells. II. The absence of ly sosomal fusion with phagocytic vacuoles containing living parasites. J. Exp. Med. 136: 1173 1194.
48. Krieger, M. 1997. The other side of scavenger receptors: pattern recognition for host defense. Curr. Opin. Lipidol. 8: 275 280.
49. Lindahl, K. F.,, D. E. Byers,, V. M. Dabhi,, R. Hovik,, E. P. Jones,, G. P. Smith,, C. R. Wang,, H. Xiao,, and M. Yoshino. 1997. H2- M3, a full-service class Ib histocompatibility antigen. Annu. Rev. Immunol. 15: 851 879.
50. Linehan, S. A.,, L. Martinez-Pomares,, and S. Gordon. 2000. Macrophage lectins in host defence. Microbes Infect. 2: 279 288.
51. Mahoney, J. A.,, and S. Gordon. 1998. Macrophage receptors and innate immunity. Biochemistry 20: 12 16.
52. Manca, C.,, S. Paul,, C. E. Barry III,, V. H. Freedman,, and G. Kaplan. 1999. Mycobacterium tuberculosis catalase and peroxidase activities and resistance to oxidative killing in human monocytes in vitro. Infect. Immun. 67: 74 79.
53. Medzhitov, R.,, and C. A. Janeway, Jr. 1997. Innate immunity: impact on the adaptive immune response. Curr. Opin. Immunol. 9: 4 9.
54. Mosser, D. M.,, and C. L. Karp. 1999. Receptor mediated subversion of macrophage cytokine production by intracellular pathogens. Curr. Opin. Immunol. 11: 406 411.
55. Ofek, I.,, J. Goldhar,, Y. Keisari,, and N. Sharon. 1995. Nonopsonic phagocytosis of microorganisms. Annu. Rev. Microbiol. 49: 239 276.
56. Paludan, S. R. 1998. Interleukin-4 and interferon-gamma: the quintessence of a mutual antagonistic relationship. Scand. J. Immunol. 48: 459 468.
57. Pamer, E.,, and P. Cresswell. 1998. Mechanisms of MHC class I— restricted antigen processing. Annu. Rev. Immunol. 16: 323 358.
58. Park, S. H.,, Y. H. Chiu,, J. Jayawardena,, J. Roark,, U. Kavita,, and A. Bendelac. 1998. Innate and adaptive functions of the CD1 pathway of antigen presentation. Semin. Immunol. 10: 391 398.
59. Peterson, P. K.,, B. J. Wilkinson,, Y. Kim,, D. Schmeling,, and P. G. Quie. 1978. Influence of encapsulation on staphylococcal opsonization and phagocytosis by human polymorphonuclear leukocytes. Infect. Immun. 19: 943 949.
60. Porcelli, S. A.,, B. W. Segelke,, M. Sugita,, I. A. Wilson,, and M. B. Brenner. 1998. The CD1 family of lipid antigen-presenting molecules. Immunol. Today 19: 362 368.
61. Portnoy, D. A.,, P. S. Jacks,, and D. J. Hinrichs. 1988. Role of hemolysin for the intracellular growth of Listeria monocytogenes. J. Exp. Med. 167: 1459 1471.
62. Pretolani, M. 1999. Interleukin-10: an anti-inflammatory cytokine with therapeutic potential. Clin. Exp. Allergy. 29: 1164 1171.
63. Rabinovitch, M. 1995. Professional and non-professional phagocytes: an introduction. Trends Cell Biol. 5: 85 87.
64. Reis e Sousa, C.,, A. Sher,, and P. Kaye. 1999. The role of dendritic cells in the induction and regulation of immunity to microbial infection. Curr. Opin. Immunol. 11: 392 399.
65. Rescigno, M.,, F. Granucci,, S. Citterio,, M. Foti,, and P. Ricciardi- Castagnoli. 1999a. Coordinated events during bacteria-induced DC maturation. Immunol. Today 20: 200 203.
66. Rescigno, M.,, F. Granucci,, and P. Ricciardi-Castagnoli. 1999b. Dendritic cells at the end of the millennium. Immunol. Cell Biol. 77: 404 410.
67. Romagnani, S. 1996. Understanding the role of Th1/Th2 cells in infection. Trends Microbiol. 4: 470 473.
68. Ross, G. D.,, and V. Vetvicka. 1993. CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multiple ligand specificities and functions. Clin. Exp. Immunol. 92: 181 184.
69. Schaible, U. E.,, H. L. Collins,, and S. H. Kaufmann. 1999. Confrontation between intracellular bacteria and the immune system. Adv. Immunol. 71: 267 377.
70. Schryvers, A. B.,, and I. Stojiljkovic. 1999. Iron acquisition systems in the pathogenic Neisseria. Mol. Microbiol. 32: 1117 1123.
71. Selvarangan, R.,, P. Goluszko,, V. Popov,, J. Singhal,, T. Pham,, D. M. Lublin,, S. Nowicki,, and B. Nowicki. 2000. Role of decay-accelerating factor domains and anchorage in internalization of Dr-fimbriated Escherichia coli. Infect. Immun. 68: 1391 1399.
72. Shiloh, M. U.,, J. D. MacMicking,, S. Nicholson,, J. E. Brause,, S. Potter,, M. Marino,, F. Fang,, M. Dinauer,, and C. Nathan. 1999. Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase. Immunity 10: 29 38.
73. Sinai, A. P.,, and K. A. Joiner. 1997. Safe haven: the cell biology of nonfusogenic pathogen vacuoles. Annu. Rev. Microbiol. 51: 415 462.
74. Storz, G.,, L. A. Tartaglia,, and B. N. Ames. 1990. The OxyR regulon. Antonie Leeuwenhoek 58: 157 161.
75. Sturgill-Koszycki, S.,, P. H. Schlesinger,, P. Chakraborty,, P. L. Haddix,, H. L. Collins,, A. K. Fok,, R. D. Allen,, S. L. Gluck,, J. Heuser,, and D. G. Russell. 1994. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton- ATPase. Science 263: 678 681. (Erratum, 263:1359.)
76. Sunder-Plassmann, G.,, S. I. Patruta,, and W. H. Horl. 1999. Pathobiology of the role of iron in infection. Am. J. Kidney Dis. 34: S25 S29.
77. Swanson, J. A.,, and S. C. Baer. 1995. Phagocytosis by zippers and triggers. Trends Cell Biol. 5: 89 93.
78. Thomson, A. (ed.). 1998. The Cytokine Handbook, 3rd ed. Academic Press, Inc., San Diego, Calif.
79. Turner, M.,, E. Schweighoffer,, F. Colucci,, J. P. Di Santo,, and V. L. Tybulewicz. 2000. Tyrosine kinase SYK: essential functions for immunoreceptor signaling. Immunol. Today 21: 148 154.
80. Underhill, D. M.,, A. Ozinsky,, A. M. Hajjar,, A. Stevens,, C. B. Wilson,, M. Bassetti,, and A. Aderem. 1999. The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401: 811 815.
81. Weinrauch, Y.,, and A. Zychlinsky. 1999. The induction of apoptosis by bacterial pathogens. Annu. Rev. Microbiol. 53: 155 187.
82. Weis, W. I.,, M. E. Taylor,, and K. Drickamer. 1998. The C-type lectin superfamily in the immune system. Immunol. Rev. 163: 19 34.
83. Whitnack, E.,, A. L. Bisno,, and E. H. Beachey. 1981. Hyaluronate capsule prevents attachment of group A streptococci to mouse peritoneal macrophages. Infect. Immun. 31: 985 991.
84. Wick, M. J.,, and H. G. Ljunggren. 1999. Processing of bacterial antigens for peptide presentation on MHC class I molecules. Immunol. Rev. 172: 153 162.
85. Wilson, M.,, R. Seymour,, and B. Henderson. 1998. Bacterial perturbation of cytokine networks. Infect. Immun. 66: 2401 2409.
86. Wright, S. D. 1999. Toll, a new piece in the puzzle of innate immunity. J. Exp. Med. 189: 605 609.
87. Wright, S. D.,, and S. C. Silverstein. 1983. Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes. J. Exp. Med. 158: 2016 2023.
88. Yewdell, J. W.,, and J. R. Bennink. 1999. Mechanisms of viral interference with MHC class I antigen processing and presentation. Annu. Rev. Cell Dev. Biol. 15: 579 606.


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Table 1

Mechanisms and examples of M functions

Citation: Brown G, Gordon S. 2002. Phagocytes and Anti-Infective Immunity, p 79-92. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch6
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Table 2

Selected cytokines important in anti-infective immunity

Citation: Brown G, Gordon S. 2002. Phagocytes and Anti-Infective Immunity, p 79-92. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch6

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