Abstract
Cytokines are small proteins or glycoproteins that transmit information from one cell to another. Most cells in the body secrete and respond to cytokines and their effects have been described on a myriad of cellular functions. Cytokine interactions may not be linear, thus making the system extremely intricate and with unpredictable features. Therefore, each model of disease may be unique, with its own mechanism of autoregulation dictated by positive and negative feedback involving cytokines and costimulatory molecules. The emergence of some cytokines over others in the course of Cryptococcus neoformans infection may characterize a positive or negative outcome of cryptococcosis. Much less is known about the influence of costimulatory molecules in regulating C. neoformans immune response. The available information indicates a critical role for proinflammatory cytokines such as tumor necrosis factor a and interleukin 12 (IL-12). The positive role of interferon γ in infected tissue as an inducer of antimicrobial function of innate immune cells and as positive feedback for IL-12 induction appears to be indisputable. In vitro studies indicate that costimulatory molecule expression appears to be regulated on antigen-presenting cells by C. neoformans and increased expression of B7-1 and CD40 on these cells may promote a protective response. These studies await confirmation in an in vivo system. The interplay between cytokines and costimulatory molecules has been scarcely explored and additional details are needed to better understand how they convey positive and negative information to immune cells in response to C. neoformans.
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Abbreviations
- APC:
-
antigen-presenting cell
- CD40L:
-
CD40 ligand
- GXM:
-
glucuronoxylomannan
- IFN:
-
interferon,
- IL:
-
interleukin
- mAb:
-
monoclonal antibody
- NK:
-
natural killer
- NO:
-
nitric oxide
- PBMC:
-
peripheral blood mononuclear cells
- Th:
-
T helper
- TNF:
-
tumor necrosis factor
References
Blackstock R., Buchanan K. L., Adesina A. M. and Murphy J. W. (1999): Differential regulation of immune response by highly and weakly virulent Cryptococcus neoformans isolates. Infect. Immun., 67, 3601 – 3609.
Casadevall A. (1995): Antibody immunity and invasive fungal infections. Infect. Immun., 63, 4211 – 4218.
Casadevall A., Cleare W., Feldmesser M., Glatman-Freedman A., Goldman D. L., Kozel T. R., Lendvai N., Mukherjee J., Pirofski L. A., Rivera J., Rosas A. L., Scharff M. D., Valadon P., Westin K. and Zhong Z. (1998): Characterization of a murine monoclonal antibody to Cryptococcus neoformans polysaccharide that is a candidate for human therapeutic studies. Antimicrob. Agents Chemother., 42, 1437 – 1446.
Casadevall A. and Perfect J. R. (1998): Cryptococcus neoformans. American Society for Microbiology Press, New York, 272 – 282.
Clumeck N., Sonnet J., Taelman H., Mascart-Lemone F., De Bruyere M., Vandeperre R, Dasnoy J., Marcelis L., Lamy M., Jonas C., Eyckmans L., Noel H., Vanhaeverbeek M. and Butzler J. P. (1984): Acquired immunodeficiency syndrome in African patients. N. Engl. J. Med., 310, 492 – 497.
Collins H. L. and Bancroft G. J. (1992): Cytokine enhancement of complement-dependent phagocytosis by macrophages: synergy of tumor necrosis-alpha and granulocyte-macrophage colony stimulating factor for phagocytosis of Cryptococcus neoformans. Eur. J. Immunol., 22, 1447 – 1454.
Cross C. E. and Bancroft G. J. (1995): Ingestion of acapsular Cryptococcus neoformans occurs via mannose and beta-glucan receptors, resulting in cytokine production and increased phagocytosis of the encapsulated form. Infect. Immun., 63, 2604 – 2611.
Cross C. E., Collins H. L. and Bancroft G. J. (1997): CR3-dependent phagocytosis by murine macrophages: different cytokines regulate ingestion of a defined CR3 ligand and complement-opsonized Cryptococcus neoformans. Immunology, 91, 289 – 296.
Decken K., Köhler G., Palmer-Lehmann K., Wunderlin A., Mattner F., Magram J., Gately M. K. and Alber G. (1998): Interleukin-12 is essential for a protective Th1 response in mice infected with Cryptococcus neoformans. Infect. Immun., 66, 4994 – 5000.
De Shaw M. and Pirofski L. A. (1995): Antibodies to the Cryptococcus neoformans capsular glucuronoxylomannan are ubiquitous in serum from HIV and HIV- individuals. Clin. Exp. Immunol., 99, 425 – 432.
Diamond R. D. and Bennet J. E. (1974): Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann. Intern. Med., 80, 176 – 181.
Dinarello C. A. (1999): Interleukin-18. Methods, 19, 121 – 132.
Feldmesser M. and Casadevall A. (1997): Effect of serum IgGI to Cryptococcus neofonnans glucuronoxylomannan on murine pulmonary infection. J. Immunol., 158, 790 – 799.
Gallis H. A., Berman R. A., Cate T. R., Hamilton J. D., Gunnells J. C. and Stickel D. L. (1975): Fungal infection following renal transplantation. Arch. Intern. Med., 135, 1163 – 1172.
Goldman D. L., Lee S. C. and Casadevall A. (1995): Tissue localization of Cryptococcus neofonnans glucuronoxylomannan in the presence and absence of specific antibody. Infect. Immun., 63, 3448 – 3453.
Gordon M. A. and Casadevall A. (1995): Serum therapy of cryptococcal meningitis. Clin. Infect. Dis., 21, 1477 – 1479.
Harrison T. S. and Levitz S. M. (1996): Role of IL-12 in peripheral blood mononuclear cell responses to fungi in persons with and without HIV infection. J. Immunol., 156, 4492 – 4497.
Harrison T. S. and Levitz S. M. (1997): Priming with IFN-y restores deficient IL-12 production by peripheral blood mononuclear cells from HIV-seropositive donors. J. Immunol., 158, 459 – 463.
Hoag K. A., Lipscomb M. F., Izzo A. A. and Street N. E. (1997): IL-12 and IFN-gamma are required for initiating the protective Thl response to pulmonary cryptococcosis in resistant C. B-17 mice. Am. J. Respir. C.ll Mol. Biol., 17, 733 – 739.
Huffnagle G. B. (1996): Role of cytokines in T cell immunity to a pulmonary Cryptococcus neoformans infection. Biol. Signals, 5, 215 – 222.
Huffnagle G. B., Boyd M. B., Street N. E. and Lipscomb M. F. (1998): IL-5 is required for eosinophil recruitment, crystal deposition, and mononuclear cell recruitment during a pulmonary Cryptococcus neoformans infection in genetically susceptible mice (C57BL/6). J. Immunol., 160, 2393 – 2400.
Huffnagle G. B., Chen G. H., Curtis J. L., McDonald R. A., Strieter R. M. and Toews G. B. (1995): Down-regulation of the afferent phase of T cell-mediated pulmonary inflammation and immunity by a high melanin-producing strain of Cryptococcus neoformans. J. Immunol., 155, 3507 – 3516.
Huffnagle G. B. and McNeil L. K. (1999): Dissemination of C. neofonnans to the central nervous system: role of chemokines, Thl immunity and leukocyte recruitment. J. Neurovirol., 5, 76 – 81.
Huffnagle G. B., Toews G. B., Burdick M. D., Boyd M. B., McAllister K. S., McDonald R. A., Kunkel S. L. and Strieter R. M. (1996): Afferent phase production of TNF-alpha is required for the development of protective T cell immunity to Cryptococcus neoformans. J. Immunol., 157, 4529 – 4536.
John G. T., Mathew M., Snehalatha E., Anandi V., Date A., Jacob C. K. and Shastry J. C. M. (1994): Cryptococcosis in renal allograft recipients. Transplantation, 58, 855 – 856.
Kawakami K., Qifeng X., Tohyama M., Qureshi M. H. and Saito A. (1996a): Contribution of tumor necrosis factor-alpha (TNF-alpha) in host defence mechanism against Cryptococcus neoformans. Clin. Exp. Immunol., 106, 468 – 474.
Kawakami K., Qureshi M. H., Koguchi Y., Nakajima K. and Saito A. (1999a): Differential effect of Cryptococcus neoformans on the production of IL-12 p40 and IL-10 by murine macrophages stimulated with lipopolysaccharide and gamma interferon. FEMS Microbiol. Lett., 175, 87 – 94.
Kawakami K., Qureshi M. H., Koguchi Y., Zhang T., Okamura H., Kurimoto M. and Saito A. (1999b): Role of TNF-alpha in the induction of fungicidal activity of mouse peritoneal exudates against Cryptococcus neoformans by IL-12 and IL-18. Cell. Immunol., 193, 9 – 16.
Kawakami K., Qureshi M. H., Zhang T., Koguki Y, Shibuya K., Naoe S. and Saito A. (1999c): Interferon-y (IFN-y)-dependent protection and synthesis of chemoattractants for mononuclear leucocytes caused by IL-12 in the lungs of mice infected with Cryptococcus neoformans. Clin. Exp. Immunol., 117, 113 – 122.
Kawakami K., Qureshi M. H., Zhang T., Koguki Y., Xie Q., Kurimoto M. and Saito A. (1999d): Interleukin-4 weakens host resistance to pulmonary and disseminated cryptococcal infection caused by combined treatment with interferon-gamma-inducing cytokines. Cell. Immunol., 197, 55 – 61.
Kawakami K., Qureshi M. H., Zhang T., Okamura H., Kurimoto M. and Saito A. (1997a): IL-18 protects mice against pulmonary and disseminated infection with Cryptococcus neoformans by inducing IFN-y production. J. Immunol., 159, 5528 – 5534.
Kawakami K., Tohyama M., Qifeng X. and Saito A. (1997b): Expression of cytokines and inducible nitric oxide synthase mRNA in the lung of mice infected with Cryptococcus neoformans: effects of interleukin-12. Infect. Immun., 65, 1307 – 1312.
Kawakami K., Tohyama M., Xie Q. and Saito A. (1996b): IL-12 protects mice against pulmonary and disseminated infection caused by Cryptococcus neoformans. Clin. Exp. Immunol., 104, 208 – 214.
Kozel T. R., Wilson M. A. and Murphy J. W. (1991): Early events in initiation of alternative complement pathway activation by the capsule of Cryptococcus neoformans. Infect. Immun., 59, 3101 – 3110.
Kozel T. R., Wilson M. A. and Welch W. H. (1992): Kinetic analysis of the amplification phase for activation and binding of C3 to encapsulated and nonencapsulated Cryptococcus neoformans. Infect. Immun., 60, 3122 – 3127.
Levitz S. M. and North E. A. (1996): Gamma interferon gene expression and release in human lymphocytes directly activated by Cryptococcus neoformans and Candida albicans. Infect. Immun., 64, 1595 – 1599.
Levitz S. M., Tabuni A., Kornfeld H., Reardon C. C. and Golenbock D. T. (1994): Production of tumor necrosis factor alpha in human leukocytes stimulated by Cryptococcus neoformans. Infect. Immun., 62, 1975 – 1981.
Levitz S. M., Tabuni A., Nong S. H. and Golenbock D. T. (1996): Effects of interleukin-10 on human peripheral blood mononuclear cell responses to Cryptococcus neoformans, Candida albicans, and lipopolysaccharide. Infect. Immun., 64, 945 – 951.
Li R. K. and Mitchell T. G. (1997): Induction of interleukin-6 mRNA in rat alveolar macrophages by in vitro exposure to both Cryptococcus neoformans and anti-C. neoformans antiserum. J. Med. Vet. Mycol., 35, 327 – 334.
Lortholary O., Improvisi L., Rayane N., Gray F., Fittinf C., Cavaillon J. M. and Dromer F. (1999): Cytokine profiles of AIDS patients are similar to those of mice with disseminated Cryptococcus neoformans infection. Infect. Immun., 67, 6314–6320.
Lovchik J. A., Lyons C. R. and Lipscomb M. F. (1995): A role for gamma interferon-induced nitric oxide in pulmonary clearance of Cryptococcus neoformans. Am. J. Respir. Cell Mol. Biol., 13, 116 – 124.
Mody C. H., Spurrell J. C. and Wood C. J. (1998): Interleukin-15 induces antimicrobial activity after release by Cryptococcus neoformans-stimulated monocytes. J. Infect. Dis., 178, 803 – 814.
Monari C., Kozel T. R., Casadevall A., Pietrella D., Palazzetti B. and Vecchiarelli A. (1999): B7 costimulatory ligand regulates development of the T-cell response to Cryptococcus neoformans. Immunology, 98, 27 – 35.
Monari C., Retini C., Palazzetti B., Bistoni F. and Vecchiarelli A. (1997): Regulatory role of exogenous IL-10 in the development of immune response versus Cryptococcus neoformans. Clin. Exp. Immunol., 109, 242 – 247.
Morel P. A. and Oriss T. B. (1998): Crossregulation between Thl and Th2 cells. Crit. Rev. Immunol., 18, 275 – 303.
Mukherjee S., Lee S., Mukherjee J., Scharff M. D. and Casadevall A. (1994): Monoclonal antibodies to Cryptococcus neoformans capsular polysaccharide modify the course of intravenous infection in mice. Infect. Immun., 62, 1079 – 1088.
Murphy J. W. and McGaba T. (1999): Blockade of CTLA-4, costimulatory molecule on the surface of T cells, enhances the protective cell-mediated immune response against Cryptococcus neoformans. In Cryptococcus and Cryptococcosis, 4h International Conference, September 12–16, 1999. Abstract n. I. 20, p. 50.
Murphy J. W., Zhou A. and Wong S. C. (1997): Direct interactions of human natural killer cells with Cryptococcus neoformans inhibit granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha production. Infect. Immun., 65, 4564 – 4571.
Rayhane N., Lortholary O., Fitting C., Callabert J., Huerre M., Dromer F. and Cavaillon J. M. (1999): Enhanced sensitivity of tumor necrosis factor/lymphotoxin-alpha-deficient mice to Cryptococcus neoformans infection despite increased levels of nitrite/nitrate, interferon–gamma, and interleukin-12. J. Infect. Dis., 180, 1637 – 1647.
Retini C., Casadevall A., Pietrella D., Monari C., Palazzetti B. and Vecchiarelli A. (1999): Specific-activated T cells regulate IL-12 production by human monocytes stimulated with Cryptococcus neoformans. J. Immunol., 162, 1618 – 1623.
Retini C., Vecchiarelli A., Monari C., Tascini C., Bistoni F. and Kozel T. R. (1996): Capsular polysaccharide of Cryptococcus neoformans induces proinflammatory cytokine release by human neutrophile. Infect. Immun., 64, 2897 – 2903.
Roseff S. A. and Levitz S. M. (1993): Effect of endothelial cells on phagocyte-mediated anticryptococcal activity. Infect. Immun., 61, 3818 – 3824.
Syme R. M.. Bruno T. F., Kozel T. R. and Mody C. H. (1999): The capsule of Cryptococcus neoformans reduces T-lymphocyte proliferation by reducing phagocytosis, which can be restored with anticapsular antibody. Infect. Immun., 67, 4620 – 4627.
Taelman H., Clerinx J., Kagame A., Batungwanayo J., Nyirabareja A. and Bogaerts J. (1991): Cryptococcosis, another growing burden for central Africa. Lancet, 338, 761.
Trinchieri G. (1998): Interleukin-12: a cytokine at the interface of inflammation and immunity. Adv. Immunol., 70, 83 – 243.
Vecchiarelli A. and Casadevall A. (1998): Antibody-mediated effects against Cryptococcus neoformans: evidence for interdependency and collaboration between humoral and cellular immunity. Res. Immunol., 149, 321 - 331.
Vecchiarelli A., Monari C., Retini C., Pietrella D., Palazzetti B., Pitzurra L. and Casadevall A. (1998a): Cryptococcus neoformans differently regulates B7-1 (CD80) and B7-2 (CD86) expression on human monocytes. Eur. J. Immunol., 28, 114 – 121.
Vecchiarelli A., Retini C., Casadevall A., Monari C., Pietrella D. and Kozel T. R. (1998b): Involvement of C3a and C5a in interleukin-8 secretion by human polymorphonuclear cells in response to capsular material of Cryptococcus neoformans. Infect. Immun., 66, 4324 – 4330.
Vecchiarelli A., Retini C., Monari C. and Casadevall A. (1998c): Specific antibody to Cryptococcus neoformans alters human leukocyte cytokine synthesis and promotes T-cell proliferation. Infect. Immun., 66, 1244 – 1247.
Vecchiarelli A., Retini C., Monari C., Tascini C., Bistoni E and Kozel T. R. (1996): Purified capsular polysaccharide of Cryptococcus neoformans induces interleukin-10 secretion by human monocytes. Infect. Immun., 64, 2846 – 2849.
Vecchiarelli A., Retini C., Pietrella D., Monari C., Tascini C., Beccari T. and Kozel T. R. (1995): Down-regulation by cryptococcal polysaccharide of tumor necrosis factor alpha and interleukin-113 secretion from human monocytes. Infect. Immun., 63, 2919 - 2923.
Walenkamp A. M., Chaka W. S., Verheul A. E, Vainshnav V. V., Cherniak R., Coenjaerts F. E. and Hoepelman I. M. (1999): Cryptococcus neoformans and its cell wall components induce similar cytokine profiles in human peripheral blood mononuclear cells despite differences in structure. FEMS Immunol. Med. Microbiol., 26, 309 – 318.
Wilson M. A. and Kozel T. R. (1992): Contribution of antibody in normal human serum to early deposition of C3 onto encapsulated and nonencapsulated Cryptococcus neoformans. Infect. Immun., 60, 754 – 761.
Yuan R., Casadevall A., Oh J. and Scharff M. D. (1997): T cells cooperate with passive antibody to modify Cryptococcus neoformans infection in mice. Proc. Natl. Acad. Sci. USA, 94, 2483 – 2488.
Zhang T., Kawakami K., Qureshi M. H., Okamura H., Kurimoto M. and Saito A. (1997): Interleukin-12 (IL-12) and IL-18 synergistically induce the fungicidal activity of murine peritoneal exudates cells against Cryptococcus neoformans through production of gamma interferon by natural killer cells. Infect. Immun., 65, 3594 – 3599.
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Vecchiarelli, A. (2001). Cytokines and Costimulatory Molecules: Positive and Negative Regulation of the Immune Response to Cryptococcus Neoformans . In: Górski, A., Krotkiewski, H., Zimecki, M. (eds) Inflammation. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9702-9_5
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DOI: https://doi.org/10.1007/978-94-015-9702-9_5
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