Complement Component C3 Is Required for Protective Innate and Adaptive Immunity to Larval Strongyloides stercoralis in Mice
Tóm tắt
This study examines the role of complement components C3 and C5 in innate and adaptive protective immunity to larval Strongyloides stercoralis in mice. Larval survival in naive C3−/− mice was increased as compared with survival in wild-type mice, whereas C3aR−/− and wild-type mice had equivalent levels of larval killing. Larval killing in naive mice was shown to be a coordinated effort between effector cells and C3. There was no difference between survival in wild-type and naive C5−/− mice, indicating that C5 was not required during the innate immune response. Naive B cell-deficient and wild-type mice killed larvae at comparable levels, suggesting that activation of the classical complement pathway was not required for innate immunity. Adaptive immunity was equivalent in wild-type and C5−/− mice; thus, C5 was also not required during the adaptive immune response. Larval killing was completely ablated in immunized C3−/− mice, even though the protective parasite-specific IgM response developed and effector cells were recruited. Protective immunity was restored to immunized C3−/− mice by transferring untreated naive serum, but not C3-depleted heat-inactivated serum to the location of the parasites. Finally, immunized C3aR−/− mice killed larvae during the adaptive immune response as efficiently as wild-type mice. Therefore, C3 was not required for the development of adaptive immunity, but was required for the larval killing process during both protective innate and adaptive immune responses in mice against larval S. stercoralis.
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Carroll, M. C.. 2004. The complement system in regulation of adaptive immunity. Nat. Immunol. 5: 981-986.
Gasque, P.. 2004. Complement: a unique innate immune sensor for danger signals. Mol. Immunol. 41: 1089-1098.
Volanakis, J. E.. 2002. The role of complement in innate and adaptive immunity. Curr. Top. Microbiol. Immunol. 266: 41-56.
Fischer, M. B., M. Ma, S. Goerg, X. Zhou, J. Xia, O. Finco, S. Han, G. Kelsoe, R. G. Howard, T. L. Rothstein, et al 1996. Regulation of the B cell response to T-dependent antigens by classical pathway complement. J. Immunol. 157: 549-556.
Pepys, M. B.. 1974. Role of complement in induction of antibody production in vivo: effect of cobra factor and other C3-reactive agents on thymus-dependent and thymus-independent antibody responses. J. Exp. Med. 140: 126-145.
Bottger, E. C., T. Hoffmann, U. Hadding, D. Bitter-Suermann. 1985. Influence of genetically inherited complement deficiencies on humoral immune response in guinea pigs. J. Immunol. 135: 4100-4107.
Drouin, S. M., D. B. Corry, J. Kildsgaard, R. A. Wetsel. 2001. Cutting edge: the absence of C3 demonstrates a role for complement in Th2 effector functions in a murine model of pulmonary allergy. J. Immunol. 167: 4141-4145.
La Flamme, A. C., A. S. MacDonald, C. R. Huxtable, M. Carroll, E. J. Pearce. 2003. Lack of C3 affects Th2 response development and the sequelae of chemotherapy in schistosomiasis. J. Immunol. 170: 470-476.
Frank, M. M., L. F. Fries. 1991. The role of complement in inflammation and phagocytosis. Immunol. Today 12: 322-326.
Hopken, U. E., B. Lu, N. P. Gerard, C. Gerard. 1996. The C5a chemoattractant receptor mediates mucosal defense to infection. Nature 383: 86-89.
Rus, H. G., F. I. Niculescu, M. L. Shin. 2001. Role of the C5b-9 complement complex in cell cycle and apoptosis. Immunol. Rev. 180: 49-55.
Porto, A. F., F. A. Neva, H. Bittencourt, W. Lisboa, R. Thompson, L. Alcantara, E. M. Carvalho. 2001. HTLV-1 decreases Th2 type of immune response in patients with strongyloidiasis. Parasite Immunol. 23: 503-507.
Neva, F. A., J. O. Filho, A. A. Gam, R. Thompson, V. Freitas, A. Melo, E. M. Carvalho. 1998. Interferon-γ and interleukin-4 responses in relation to serum IgE levels in persons infected with human T lymphotropic virus type I and Strongyloides stercoralis. J. Infect. Dis. 178: 1856-1859.
Kerepesi, L. A., T. J. Nolan, G. A. Schad, S. Lustigman, D. R. Herbert, P. B. Keiser, T. B. Nutman, A. J. Krolewiecki, D. Abraham. 2004. Human immunoglobulin G mediates protective immunity and identifies protective antigens against larval Strongyloides stercoralis in mice. J. Infect. Dis. 189: 1282-1290.
Abraham, D., H. L. Rotman, H. F. Haberstroh, W. Yutanawiboonchai, R. A. Brigandi, O. Leon, T. J. Nolan, G. A. Schad. 1995. Strongyloides stercoralis: protective immunity to third-stage larvae in BALB/cByJ mice. Exp. Parasitol. 80: 297-307.
Herbert, D. R., T. J. Nolan, G. A. Schad, D. Abraham. 2002. The role of B cells in immunity against larval Strongyloides stercoralis in mice. Parasite Immunol. 24: 95-101.
Rotman, H. L., S. Schnyder-Candrian, P. Scott, T. J. Nolan, G. A. Schad, D. Abraham. 1997. IL-12 eliminates the Th-2 dependent protective immune response of mice to larval Strongyloides stercoralis. Parasite Immunol. 19: 29-39.
Herbert, D. R., J. J. Lee, N. A. Lee, T. J. Nolan, G. A. Schad, D. Abraham. 2000. Role of IL-5 in innate and adaptive immunity to larval Strongyloides stercoralis in mice. J. Immunol. 165: 4544-4551.
Brigandi, R. A., H. L. Rotman, W. Yutanawiboonchai, O. Leon, T. J. Nolan, G. A. Schad, D. Abraham. 1996. Strongyloides stercoralis: role of antibody and complement in immunity to the third stage of larvae in BALB/cByJ mice. Exp. Parasitol. 82: 279-289.
Ligas, J. A., L. A. Kerepesi, A. M. Galioto, S. Lustigman, T. J. Nolan, G. A. Schad, D. Abraham. 2003. Specificity and mechanism of immunoglobulin M (IgM)- and IgG-dependent protective immunity to larval Strongyloides stercoralis in mice. Infect. Immun. 71: 6835-6843.
De Messias, I. J., R. M. Genta, W. D. Mohren. 1994. Adherence of monocytes and polymorphonuclear cells to infective larvae of Strongyloides stercoralis after complement activation. J. Parasitol. 80: 267-274.
Humbles, A. A., B. Lu, C. A. Nilsson, C. Lilly, E. Israel, Y. Fujiwara, N. P. Gerard, C. Gerard. 2000. A role for the C3a anaphylatoxin receptor in the effector phase of asthma. Nature 406: 998-1001.
Hanski, C., M. Naumann, A. Grutzkau, G. Pluschke, B. Friedrich, H. Hahn, E. O. Riecken. 1991. Humoral and cellular defense against intestinal murine infection with Yersinia enterocolitica. Infect. Immun. 59: 1106-1111.
Herbert, D. R., T. J. Nolan, G. A. Schad, S. Lustigman, D. Abraham. 2002. Immunoaffinity-isolated antigens induce protective immunity against larval Strongyloides stercoralis in mice. Exp. Parasitol. 100: 112-120.
Boes, M.. 2000. Role of natural and immune IgM antibodies in immune responses. Mol. Immunol. 37: 1141-1149.
Ferreira, A. M., M. Breijo, R. B. Sim, A. Nieto. 2000. Contribution of C5-mediated mechanisms to host defense against Echinococcus granulosus hydatid infection. Parasite Immunol. 22: 445-453.
Heyman, B., L. Pilstrom, M. J. Shulman. 1988. Complement activation is required for IgM-mediated enhancement of the antibody response. J. Exp. Med. 167: 1999-2004.
Ward, P. A., L. J. Newman. 1969. A neutrophil chemotactic factor from human C′5. J. Immunol. 102: 93-99.
Henson, P. M.. 1971. The immunologic release of constituents from neutrophil leukocytes. I. The role of antibody and complement on nonphagocytosable surfaces or phagocytosable particles. J. Immunol. 107: 1535-1546.
Grove, D. I., C. Northern, H. J. Dawkins. 1985. Interactions of Strongyloides ratti free-living and skin-penetrated infective larvae and parasitic adults with serum and cells in vitro. Aust. J. Exp. Biol. Med. Sci. 63: 521-529.
Shaio, M. F., S. C. Hou, J. G. Chen, C. C. Wu, K. D. Yang, F. Y. Chang. 1990. Immunoglobulin G-dependent classical complement pathway activation in neutrophil-mediated cytotoxicity to infective larvae of Angiostrongylus cantonensis. Ann. Trop. Med. Parasitol. 84: 185-191.
Anwar, A. R., S. R. Smithers, A. B. Kay. 1979. Killing of schistosomula of Schistosoma mansoni coated with antibody and/or complement by human leukocytes in vitro: requirement for complement in preferential killing by eosinophils. J. Immunol. 122: 628-637.
Klaver-Wesseling, J. C., J. C. Vetter, E. N. Schoeman. 1982. The in-vitro interaction between several components of the canine immune system and infective larvae of Ancylostoma caninum. Parasite Immunol. 4: 227-232.
Dempsey, P. W., M. E. Allison, S. Akkaraju, C. C. Goodnow, D. T. Fearon. 1996. C3d of complement as a molecular adjuvant: bridging innate and acquired immunity. Science 271: 348-350.
Ahearn, J. M., M. B. Fischer, D. Croix, S. Goerg, M. Ma, J. Xia, X. Zhou, R. G. Howard, T. L. Rothstein, M. C. Carroll. 1996. Disruption of the Cr2 locus results in a reduction in B-1a cells and in an impaired B cell response to T-dependent antigen. Immunity 4: 251-262.
Rainbird, M. A., D. Macmillan, E. N. Meeusen. 1998. Eosinophil-mediated killing of Haemonchus contortus larvae: effect of eosinophil activation and role of antibody, complement and interleukin-5. Parasite Immunol. 20: 93-103.
Kildsgaard, J., T. J. Hollmann, K. W. Matthews, K. Bian, F. Murad, R. A. Wetsel. 2000. Cutting edge: targeted disruption of the C3a receptor gene demonstrates a novel protective anti-inflammatory role for C3a in endotoxin-shock. J. Immunol. 165: 5406-5409.
Legler, D. F., M. Loetscher, S. A. Jones, C. A. Dahinden, M. Arock, B. Moser. 1996. Expression of high- and low-affinity receptors for C3a on the human mast cell line, HMC-1. Eur. J. Immunol. 26: 753-758.
Daffern, P. J., P. H. Pfeifer, J. A. Ember, T. E. Hugli. 1995. C3a is a chemotaxin for human eosinophils but not for neutrophils. I. C3a stimulation of neutrophils is secondary to eosinophil activation. J. Exp. Med. 181: 2119-2127.
Kawamoto, S., A. Yalcindag, D. Laouini, S. Brodeur, P. Bryce, B. Lu, A. A. Humbles, H. Oettgen, C. Gerard, R. S. Geha. 2004. The anaphylatoxin C3a down-regulates the Th2 response to epicutaneously introduced antigen. J. Clin. Invest. 114: 399-407.
Scribner, D. J., D. Fahrney. 1976. Neutrophil receptors for IgG and complement: their roles in the attachment and ingestion phases of phagocytosis. J. Immunol. 116: 892-897.
Goldstein, I. M., H. B. Kaplan, A. Radin, M. Frosch. 1976. Independent effects of IgG and complement upon human polymorphonuclear leukocyte function. J. Immunol. 117: 1282-1287.
Xia, Y., V. Vetvicka, J. Yan, M. Hanikyrova, T. Mayadas, G. D. Ross. 1999. The β-glucan-binding lectin site of mouse CR3 (CD11b/CD18) and its function in generating a primed state of the receptor that mediates cytotoxic activation in response to iC3b-opsonized target cells. J. Immunol. 162: 2281-2290.
Vetvicka, V., B. P. Thornton, G. D. Ross. 1996. Soluble β-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells. J. Clin. Invest. 98: 50-61.