Chapter 6 : Phagocytes and Anti-Infective Immunity

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in

Phagocytes and Anti-Infective Immunity, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817978/9781555812140_Chap06-1.gif /docserver/preview/fulltext/10.1128/9781555817978/9781555812140_Chap06-2.gif


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

Key Concept Ranking

Infection and Immunity
Immune Systems
Adaptive Immune System
Major Histocompatibility Complex
Innate Immune System
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
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
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
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
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
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
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
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
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Aderem, A.,, and D. M. Underhill. 1999. Mechanisms of phagocytosis in macrophages. Annu. Rev. Immunol. 17:593623.
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. 134:713740.
3. Banchereau, J.,, and R. M. Steinman. 1998. Dendritic cells and the control of immunity. Nature 392:245252.
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. 186:11591163.
6. Bell, D.,, J. W. Young,, and J. Banchereau. 1999. Dendritic cells. Adv. Immunol. 72:255324.
7. Berón, W.,, C. Alvarez-Dominguez,, L. Mayorga,, and P. D. Stahl. 1995. Membrane trafficking along the phagocytic pathway. Trends Cell Biol. 5:100104.
8. Billiau, A.,, H. Heremans,, K. Vermeire,, and P. Matthys. 1998. Immunomodulatory properties of interferon-gamma. An update. Ann. N. Y. Acad. Sci. 856:2232.
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. 10:383390.
10. Blackwell, J. M.,, and S. Searle. 1999. Genetic regulation of macrophage activation: understanding the function of Nramp1 (=Ity /Lsh/ Bcg). Immunol. Lett. 65:7380.
11. Burgner, D.,, K. Rockett,, and D. Kwiatkowski. 1999. Nitric oxide and infectious diseases. Arch. Dis. Child. 81:185188.
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. 172:163169.
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 111:283289.
14. Chang, K. P.,, and D. M. Dwyer. 1976. Multiplication of a human parasite (Leishmania donovani) in phagolysosomes of hamster macrophages in vitro. Science 193:678680.
15. Clark, R. A. 1999. Activation of the neutrophil respiratory burst oxidase. J. Infect. Dis. 179(Suppl. 2):S309S317.
16. Cornelis, G. R. 1998. The Yersinia deadly kiss. J. Bacteriol. 180:54955504.
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. 17:37973806.
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 97:680685.
20. Cresswell, P. 1994. Assembly, transport, and function of MHC class II molecules. Annu. Rev. Immunol. 12:259293.
21. Descoteaux, A.,, and S. J. Turco. 1999. Glycoconjugates in Leishmania infectivity. Biochim. Biophys. Acta 1455:341352.
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. 124:677688.
23. De Voss, J. J.,, K. Rutter,, B. G. Schroeder,, and C. E. Barry III. 1999. Iron acquisition and metabolism by mycobacteria. J. Bacteriol. 181:44434451.
24. Ehlers, M. R.,, and M. Daffe. 1998. Interactions between Mycobacterium tuberculosis and host cells: are mycobacterial sugars the key? Trends Microbiol. 6:328335.
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. 63:31173124.
26. Fearon, D. T.,, and R. M. Locksley. 1996. The instructive role of innate immunity in the acquired immune response. Science 272:5053.
27. Fenton, M. J.,, and D. T. Golenbock. 1998. LPS-binding proteins and receptors. J. Leukoc. Biol. 64:2532.
28. Finlay, B. B.,, and S. Falkow. 1997. Common themes in microbial pathogenicity revisited. Microbiol. Mol. Biol. Rev. 61:136169.
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. 7:232236.
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. 66:763764.
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. 5:216223.
33. Gordon, S., 1999a. Macrophages and the immune response, p. 533545. 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. 191:515528.
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. 142:12631282.
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. 144:788809.
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. 185:717730.
40. Hampton, M. B.,, A. J. Kettle,, and C. C. Winterbourn. 1998. Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. Blood 92:30073017.
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. 64:796809.
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. 9:745772.
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. 11:19911999.
44. Horwitz, M. A. 1983. Formation of a novel phagosome by the Legionnaires’ disease bacterium (Legionella pneumophila) in human monocytes. J. Exp. Med. 158:13191331.
45. Horwitz, M. A. 1984. Phagocytosis of the Legionnaires’ disease bacterium (Legionella pneumophila) occurs by a novel mechanism: engulfment within a pseudopod coil. Cell 36:2733.
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. 56:18801889.
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. 136:11731194.
48. Krieger, M. 1997. The other side of scavenger receptors: pattern recognition for host defense. Curr. Opin. Lipidol. 8:275280.
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. 15:851879.
50. Linehan, S. A.,, L. Martinez-Pomares,, and S. Gordon. 2000. Macrophage lectins in host defence. Microbes Infect. 2:279288.
51. Mahoney, J. A.,, and S. Gordon. 1998. Macrophage receptors and innate immunity. Biochemistry 20:1216.
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. 67:7479.
53. Medzhitov, R.,, and C. A. Janeway, Jr. 1997. Innate immunity: impact on the adaptive immune response. Curr. Opin. Immunol. 9:49.
54. Mosser, D. M.,, and C. L. Karp. 1999. Receptor mediated subversion of macrophage cytokine production by intracellular pathogens. Curr. Opin. Immunol. 11:406411.
55. Ofek, I.,, J. Goldhar,, Y. Keisari,, and N. Sharon. 1995. Nonopsonic phagocytosis of microorganisms. Annu. Rev. Microbiol. 49:239276.
56. Paludan, S. R. 1998. Interleukin-4 and interferon-gamma: the quintessence of a mutual antagonistic relationship. Scand. J. Immunol. 48:459468.
57. Pamer, E.,, and P. Cresswell. 1998. Mechanisms of MHC class I— restricted antigen processing. Annu. Rev. Immunol. 16:323358.
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. 10:391398.
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. 19:943949.
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 19:362368.
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. 167:14591471.
62. Pretolani, M. 1999. Interleukin-10: an anti-inflammatory cytokine with therapeutic potential. Clin. Exp. Allergy. 29:11641171.
63. Rabinovitch, M. 1995. Professional and non-professional phagocytes: an introduction. Trends Cell Biol. 5:8587.
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. 11:392399.
65. Rescigno, M.,, F. Granucci,, S. Citterio,, M. Foti,, and P. Ricciardi- Castagnoli. 1999a. Coordinated events during bacteria-induced DC maturation. Immunol. Today 20:200203.
66. Rescigno, M.,, F. Granucci,, and P. Ricciardi-Castagnoli. 1999b. Dendritic cells at the end of the millennium. Immunol. Cell Biol. 77:404410.
67. Romagnani, S. 1996. Understanding the role of Th1/Th2 cells in infection. Trends Microbiol. 4:470473.
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. 92:181184.
69. Schaible, U. E.,, H. L. Collins,, and S. H. Kaufmann. 1999. Confrontation between intracellular bacteria and the immune system. Adv. Immunol. 71:267377.
70. Schryvers, A. B.,, and I. Stojiljkovic. 1999. Iron acquisition systems in the pathogenic Neisseria. Mol. Microbiol. 32:11171123.
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. 68:13911399.
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 10:2938.
73. Sinai, A. P.,, and K. A. Joiner. 1997. Safe haven: the cell biology of nonfusogenic pathogen vacuoles. Annu. Rev. Microbiol. 51:415462.
74. Storz, G.,, L. A. Tartaglia,, and B. N. Ames. 1990. The OxyR regulon. Antonie Leeuwenhoek 58:157161.
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 263:678681. (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:S25S29.
77. Swanson, J. A.,, and S. C. Baer. 1995. Phagocytosis by zippers and triggers. Trends Cell Biol. 5:8993.
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 21:148154.
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 401:811815.
81. Weinrauch, Y.,, and A. Zychlinsky. 1999. The induction of apoptosis by bacterial pathogens. Annu. Rev. Microbiol. 53:155187.
82. Weis, W. I.,, M. E. Taylor,, and K. Drickamer. 1998. The C-type lectin superfamily in the immune system. Immunol. Rev. 163:1934.
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. 31:985991.
84. Wick, M. J.,, and H. G. Ljunggren. 1999. Processing of bacterial antigens for peptide presentation on MHC class I molecules. Immunol. Rev. 172:153162.
85. Wilson, M.,, R. Seymour,, and B. Henderson. 1998. Bacterial perturbation of cytokine networks. Infect. Immun. 66:24012409.
86. Wright, S. D. 1999. Toll, a new piece in the puzzle of innate immunity. J. Exp. Med. 189:605609.
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. 158:20162023.
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. 15:579606.


Generic image for table
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
Generic image for table
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

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error