Chapter 29 : Interactions of Capsule with Antibody and Complement

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Interactions of Capsule with Antibody and Complement, Page 1 of 2

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Glucuronoxylomannan (GXM) is the most prominent of the capsular constituents and is the primary target for anticapsular antibody and the most likely mediator of capsule-complement interactions. The goal of this chapter is to describe (i) variability in the interactions of GXM antibodies with the capsular matrix, (ii) the mechanisms for interaction of the capsule with proteins of the complement system, (iii) the nexus of the anticapsular antibody and complement system in capsule interactions, and (iv) the consequences of antibody and complement binding for modification of the capsular matrix. Differential interference contrast (DIC) systems detect optical gradients, preserve its sign, and convert the gradients into visible intensity gradients. Binding of antibody to the capsule edge to produce the annular rim could be due to localization of epitopes only at the capsule perimeter; monoclonal antibodies (MAbs) producing puffy patterns may bind to epitopes located throughout the capsule. Evidence of the importance of the complement system is provided in several reports of the course of cryptococcosis in normal versus complement deficient mice. Activation of the alternative pathway leads to conversion of C3 to C3b, which in turn, binds to the cryptococcal cell. Incubation of acapsular cryptococci in adsorbed serum leads to deposition of C3 onto the cell wall, but C3 binding occurs via the slow kinetics characteristic of the alternative pathway. In contrast, encapsulated cryptococci are unable to adsorb the antibodies from normal serum that mediate the rapid, early deposition of C3 onto acapsular cryptococci.

Citation: Kozel T. 2011. Interactions of Capsule with Antibody and Complement, p 409-415. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch29

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1. Casadevall,, A.,, J. Mukherjee,, S. J. N. Devi,, R. Schneerson, J. B. Robbins, and, M. D. Scharff. 1992. Antibodies elicited by a Cryptococcus neoformans-tetanus toxoid conjugate vaccine have the same specificity as those elicited in infection. J. Infect. Dis. 165:10861093.
2. Diamond,, R. D.,, J. E. May,, M. Kane, M. M. Frank, and, J. E. Bennett. 1973. The role of late complement components and the alternate complement pathway in experimental cryptococcosis. Proc. Soc. Exp. Biol. Med. 144:312315.
3. Diamond,, R. D.,, J. E. May,, M. A. Kane,, M. M. Frank, and, J. E. Bennett. 1974. The role of the classical and alternate complement pathways in host defenses against Cryptococcus neoformans infection. J. Immunol. 112:22602270.
4. Dromer, F.,, C. Perronne,, J. Barge, J. L. Vilde, and, P. Yeni. 1989. Role of IgG and complement component C5 in the initial course of experimental cryptococcosis. Clin. Exp. Immunol. 78:412417.
5. Dromer,, F.,, J. Salamero,, A. Contrepois,, C. Carbon,, and P. Yeni. 1987. Production, characterization, and antibody specificity of a mouse monoclonal antibody reactive with Cryptococcus neoformans capsular polysaccharide. Infect. Immun. 55:742748.
6. Eckert, T. F., and, T. R. Kozel. 1987. Production and characterization of monoclonal antibodies specific for Cryptococcus neoformans capsular polysaccharide. Infect. Immun. 55:18951899.
7. Eisen,, D. P.,, M. M. Dean,, M. V. O’Sullivan,, S. Heatley, and, R. M. Minchinton. 2008. Mannosebinding lectin deficiency does not appear to predispose to cryptococcosis in nonimmunocompromised patients. Med. Mycol. 46:371375.
8. Evans, E. E. 1950. The antigenic composition of Cryptococcus neoformans. I. A serologic classification by means of the capsular and agglutination reactions. J. Immunol. 64:423430.
9. Gates, M. A., and, T. R. Kozel. 2006. Differential localization of complement component 3 within the capsular matrix of Cryptococcus neoformans. Infect. Immun. 74:30963106.
10. Gates, M. A.,, P. Thorkildson, and, T. R. Kozel. 2004. Molecular architecture of the Cryptococcus neoformans capsule. Mol. Microbiol. 52:1324.
11. Goren, M. B., and, J. Warren. 1968. Immunofluorescence studies of reactions at the cryptococcal capsule. J. Infect. Dis. 118:215229.
12. Graybill, J. R., and, J. Ahrens. 1981. Immunization and complement interaction in host defence against murine cryptococcosis. J. Reticuloendothel. Soc. 30:347357.
13. Kozel,, T. R.,, B. C. H. deJong,, M. M. Grinsell,, R. S. MacGill, and, K. K. Wall. 1998. Characterization of anticapsular monoclonal antibodies that regulate activation of the complement system by the Cryptococcus neoformans capsule. Infect. Immun. 66:15381546.
14. Kozel, T. R., and, J. L. Follette. 1981. Opsonization of encapsulated Cryptococcus neoformans by specific anticapsular antibody. Infect. Immun. 31:978984.
15. Kozel, T. R.,, R. S. MacGill, and, K. K. Wall. 1998. Bivalency is required for anti-capsular monoclonal antibodies to optimally suppress activation of the alternative complement pathway by the Cryptococcus neoformans capsule. Infect. Immun. 66:15471553.
16. Kozel, T. R., and, G. S. T. Pfrommer. 1986. Activation of the complement system by Cryptococcus neoformans leads to binding of iC3b to the yeast. Infect. Immun. 52:15.
17. Kozel,, T. R.,, G. S. T. Pfrommer,, A. S. Guerlain,, B. A. Highison, and, G. J. Highison. 1988. Strain variation in phagocytosis of Cryptococcus neoformans: dissociation of susceptibility to phagocytosis from activation and binding of op-sonic fragments of C3. Infect. Immun. 56:27942800.
18. Kozel,, T. R.,, P. Thorkildson,, S. Brandt,, W. H. Welch,, J. A. Lovchik,, D. P. AuCoin,, J. Vilai, and, C. R. Lyons. 2007. Protective and immunochemical activities of monoclonal antibodies reactive with the Bacillus anthracis polypeptide capsule. Infect. Immun. 75:152163.
19. Kozel, T. R.,, L. C. Weinhold, and, D. M. Lupan. 1996. Distinct characteristics of initiation of the classical and alternative complement pathways by Candida albicans. Infect. Immun. 64:33603368.
20. Kozel,, T. R.,, M. A. Wilson,, T. P. Farrell, and, S. M. Levitz. 1989. Activation of C3 and binding to Aspergillus fumigatus conidia and hyphae. Infect. Immun. 57:34123417.
21. Kozel, T. R.,, M. A. Wilson, and, J. W. Murphy. 1991. Early events in initiation of alternative complement pathway activation by the capsule of Cryptococcus neoformans. Infect. Immun. 59:31013110.
22. Kozel,, T. R.,, M. A. Wilson,, G. S. T. Pfrommer, and, A. M. Schlageter. 1989. Activation and binding of op-sonic fragments of C3 on encapsulated Cryptococcus neoformans by using an alternative complement pathway reconstituted from six isolated proteins. Infect. Immun. 57:19221927.
23. Law, S. K., and, R. P. Levine. 1977. Interaction between the third complement protein and cell surface macromolecules. Proc. Natl. Acad. Sci. USA 74:27012705.
24. Law, S. K.,, N. A. Lichtenberg, and, R. P. Levine. 1979. Evidence for an ester linkage between the labile binding site of C3b and receptive surfaces. J. Immunol. 123:13881394.
25. Levitz, S. M., and, A. Tabuni. 1991. Binding of Cryptococcus neoformans by human cultured mac-rophages: requirements for multiple complement receptors and actin. J. Clin. Invest. 87:528535.
26. Levitz, S. M.,, A. Tabuni, and, C. Treseler. 1993. Effect of mannosebinding protein on binding of Cryptococcus neoformans to human phagocytes. Infect. Immun. 61:48914893.
27. Lovchik, J. A., and, M. F. Lipscomb. 1993. Role of C5 and neutrophils in the pulmonary intravascular clearance of circulating Cryptococcus neoformans. J. Respir. Cell Mol. Biol. 9:617627.
28. MacGill,, T. C.,, R. S. MacGill,, A. Casadevall, and, T. R. Kozel. 2000. Biological correlates of capsular (quellung) reactions of Cryptococcus neoformans. J. Immunol. 164:48354842.
29. Macura, N.,, T. Zhang, and, A. Casadevall. 2007. Dependence of macrophage phagocytic efficacy on antibody concentration. Infect. Immun. 75:19041915.
30. Maitta,, R. W.,, K. Datta,, Q. Chang,, R. X. Luo,, B. Witover,, K. Subramaniam, and, L. A. Pirofski. 2004. Protective and nonprotective human immunoglobulin M monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan manifest different specificities and gene use profiles. Infect. Immun. 72:48104818.
31. Martinez, L. R.,, D. Moussai, and, A. Casadevall. 2004. Antibody to Cryptococcus neoformans glucuronoxylomannan inhibits the release of capsular antigen. Infect. Immun. 72:36743679.
32. Maxson, M. E.,, E. Cook,, A. Casadevall, and, O. Zaragoza. 2007. The volume and hydration of the Cryptococcus neoformans polysaccharide capsule. Fungal. Genet. Biol. 44:180186.
33. Maxson,, M. E.,, E. Dadachova,, A. Casadevall,, and O. Zaragoza. 2007. Radial mass density, charge, and epitope distribution in the Cryptococcus neoformans capsule. Eukaryot. Cell 6:95109.
34. Mershon,, K. L.,, A. Vasuthasawat, G. W. Lawson,, S. L. Morrison, and, D. O. Beenhouwer. 2009. Role of complement in protection against Cryptococcus gattii infection. Infect. Immun. 77:10611070.
35. Mukherjee, J.,, W. Cleare, and, A. Casadevall. 1995. Monoclonal antibody mediated capsular reactions (quellung) in Cryptococcus neoformans. J. Immunol. Methods 184:139143.
36. Mukherjee, J.,, T. R. Kozel, and, A. Casadevall. 1999. Monoclonal antibodies reveal additional epitopes of serotype D Cryptococcus neoformans capsular glucuronoxylomannan that elicit protective antibodies. J. Immunol. 161:35573568.
37. Mukherjee, J.,, S. C. Lee, and, A. Casadevall. 1995. Antibodies to Cryptococcus neoformans glucuronoxylomannan enhance antifungal activity of murine mac-rophages. Infect. Immun. 63:573579.
38. Mukherjee, J.,, G. Nussbaum,, M. D. Scharff, and, A. Casadevall. 1995. Protective and nonprotective monoclonal antibodies to Cryptococcus neoformans originating from one B-cell. J. Exp. Med. 181:405409.
39. Neill,, J. M.,, C. G. Castillo,, R. H. Smith, and, C. E. Kapros. 1949. Capsular reactions and soluble antigens of Torula histolytica and of Sporotrichum schenckii. J. Exp. Med. 89:93106.
40. Netski, D., and, T. R. Kozel. 2002. Fc-dependent and Fc-independent opsonization of Cryptococcus neoformans by anticapsular monoclonal antibodies: importance of epitope specificity. Infect. Immun. 70:28122819.
41. Nussbaum, G.,, W. Cleare,, A. Casadevall, M. D. Scharff, and, P. Valadon. 1997. Epitope location in the Cryptococcus neoformans capsule is a determinant of antibody efficacy. J. Exp. Med. 185:685695.
42. Panepinto,, J. C.,, K. W. Komperda,, M. Hacham,, S. Shin,, X. Liu, and, P. R. Williamson. 2007. Binding of serum mannan binding lectin to a cell integritydefective Cryptococcus neoformans ccr4 Δ mutant. Infect. Immun. 75:47694779.
43. Pfrommer,, G. S. T.,, S. M. Dickens,, M. A. Wilson,, B. J. Young, and, T. R. Kozel. 1993. Accelerated decay of C3b to iC3b when C3b is bound to the Cryptococcus neoformans capsule. Infect. Immun. 61:43604366.
44. Rakesh,, V.,, A. D. Schweitzer,, O. Zaragoza,, R. Bryan,, K. Wong,, A. Datta,, A. Casadevall, and, E. Dadachova. 2008. Finiteelement model of interaction between fungal polysaccharide and monoclonal antibody in the capsule of Cryptococcus neoformans. J. Phys. Chem. B 112:85148522.
45. Rhodes, J. C. 1985. Contribution of complement component C5 to the pathogenesis of experimental murine cryptococcosis. Sabouraudia 23:225234.
46. Schelenz,, S.,, R. Malhotra,, R. B. Sim,, U. Holmskov, and, G. J. Bancroft. 1995. Binding of host collectins to the pathogenic yeast Cryptococcus neoformans: human surfactant protein D acts as an agglutinin for acapsular yeast cells. Infect. Immun. 63:33603366.
47. Taborda, C. P., and, A. Casadevall. 2002. CR3 (CD11b/CD18) and CR4 (CD11c/CD18) are involved in complementindependent antibodymediated phagocytosis of Cryptococcus neoformans. Immunity 16:791802.
48. Taborda, C. P., and, A. Casadevall. 2001. Immunoglobulin M efficacy against Cryptococcus neoformans: mechanism, dose dependence, and prozonelike effects in passive protection experiments. J. Immunol. 166:21002107.
49. Taborda, C. P.,, J. Rivera,, O. Zaragoza, and, A. Casadevall. 2003. More is not necessarily better: prozonelike effects in passive immunization with IgG. J. Immunol. 170:36213630.
50. van Asbeck,, E. C.,, A. I. Hoepelman,, J. Scharringa, B. L. Herpers, and, J. Verhoef. 2008. Mannose binding lectin plays a crucial role in innate immunity against yeast by enhanced complement activation and enhanced uptake of polymorphonuclear cells. BMC Microbiol. 8:229.
51. Van den Berg, C. W.,, P. C. Aerts, and, H. van Dijk. 1991. In vivo anticomplementary activities of the cobra venom factors from Naja naja and Naja haje. J. Immunol. Methods 136:287294.
52. Vecchiarelli, A. 2000. Immunoregulation by capsular components of Cryptococcus neoformans. Med. Mycol. 38:407417.
53. Wilson, M. A., and, T. R. Kozel. 1992. Contribution of antibody in normal human serum to early deposition of C3 onto encapsulated and nonencapsulated Cryptococcus neoformans. Infect. Immun. 60:754761.
54. Young, B. J., and, T. R. Kozel. 1993. Effects of strain variation, serotype and structural modification on the kinetics for activation and binding of C3 to Cryptococcus neoformans. Infect. Immun. 61:29662972.
55. Zaragoza, O., and, A. Casadevall. 2006. Monoclonal antibodies can affect complement deposition on the capsule of the pathogenic fungus Cryptococcus neoformans by both classical pathway activation and steric hindrance. Cell Microbiol. 8:18621876.
56. Zarogoza, O.,, C. P. Taborda, and, A. Casadevall. 2003. The efficacy of complementmediated phagocytosis of Cryptococcus neoformans is dependent on the location of C3 in the polysaccharide capsule and involves both direct and indirect C3-mediated interactions. Eur. J. Immunol. 33:19571967.

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