Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Jan;65(1):272–278. doi: 10.1128/iai.65.1.272-278.1997

Cryptococcus neoformans and cryptococcal glucuronoxylomannan, galactoxylomannan, and mannoprotein induce different levels of tumor necrosis factor alpha in human peripheral blood mononuclear cells.

W Chaka 1, A F Verheul 1, V V Vaishnav 1, R Cherniak 1, J Scharringa 1, J Verhoef 1, H Snippe 1, I M Hoepelman 1
PMCID: PMC174587  PMID: 8975923

Abstract

Tumor necrosis factor alpha (TNF-alpha) release by peripheral blood mononuclear cells (PBMC) during disseminated infection by Cryptococcus neoformans may initiate and amplify the immune response of the host, leading to elimination of the fungus. The ability to induce TNF-alpha in PBMC by four clinical strains of C. neoformans, a laboratory strain (NIH 37), and the purified cryptococcal components glucuronoxylomannan (GXM), galactoxylomannan (GalXM), and mannoproteins (MP1 and MP2) were investigated under different opsonic conditions. In the absence of serum, the levels of TNF-alpha induced by all strains and cryptococcal components were not above background levels. Normal human serum (NHS) enhanced TNF-alpha induction by whole cryptococci and the different cryptococcal components, with MP2 being the most potent TNF-alpha inducer. Inactivation of complement (HI NHS) almost abrogated the ability of whole cryptococci and the GXMs to induce TNF-alpha. In contrast, when MP1, MP2, and GalXM were incubated with HI NHS, 48, 71, and 44%, respectively, of the original TNF-alpha levels remained. MPs incubated with heat-inactivated immunoglobulin G (IgG)-depleted serum still induced 50% of the levels of TNF-alpha induced by components incubated with HI NHS. Both these sera contained the same very low levels of anti-MP IgG antibodies, indicating the opsonic effect of a heat-stable factor other than antibody. Two anti-CD14 monoclonal antibodies (60BCA and 3C10) inhibited the production of TNF-alpha induced by MP2. The results indicate that (i) induction of TNF-alpha by C. neoformans and GXMs strongly depends on complement, (ii) MP1 and MP2 induction of TNF-alpha is facilitated by a heat-stable serum factor other than Ig, and (iii) CD14 may be involved in the induction of TNF-alpha by MP2.

Full Text

The Full Text of this article is available as a PDF (228.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ausiello C. M., Urbani F., Gessani S., Spagnoli G. C., Gomez M. J., Cassone A. Cytokine gene expression in human peripheral blood mononuclear cells stimulated by mannoprotein constituents from Candida albicans. Infect Immun. 1993 Oct;61(10):4105–4111. doi: 10.1128/iai.61.10.4105-4111.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barnes P. F., Chatterjee D., Abrams J. S., Lu S., Wang E., Yamamura M., Brennan P. J., Modlin R. L. Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure. J Immunol. 1992 Jul 15;149(2):541–547. [PubMed] [Google Scholar]
  3. Beutler B., Cerami A. Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature. 1986 Apr 17;320(6063):584–588. doi: 10.1038/320584a0. [DOI] [PubMed] [Google Scholar]
  4. Cherniak R., Morris L. C., Anderson B. C., Meyer S. A. Facilitated isolation, purification, and analysis of glucuronoxylomannan of Cryptococcus neoformans. Infect Immun. 1991 Jan;59(1):59–64. doi: 10.1128/iai.59.1.59-64.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cherniak R., Sundstrom J. B. Polysaccharide antigens of the capsule of Cryptococcus neoformans. Infect Immun. 1994 May;62(5):1507–1512. doi: 10.1128/iai.62.5.1507-1512.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Collins H. L., Bancroft G. J. Cytokine enhancement of complement-dependent phagocytosis by macrophages: synergy of tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor for phagocytosis of Cryptococcus neoformans. Eur J Immunol. 1992 Jun;22(6):1447–1454. doi: 10.1002/eji.1830220617. [DOI] [PubMed] [Google Scholar]
  7. Collins H. L., Bancroft G. J. Encapsulation of Cryptococcus neoformans impairs antigen-specific T-cell responses. Infect Immun. 1991 Nov;59(11):3883–3888. doi: 10.1128/iai.59.11.3883-3888.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Diamond R. D., May J. E., Kane M. A., Frank M. M., Bennett J. E. The role of the classical and alternate complement pathways in host defenses against Cryptococcus neoformans infection. J Immunol. 1974 Jun;112(6):2260–2270. [PubMed] [Google Scholar]
  9. Djeu J. Y., Blanchard D. K., Richards A. L., Friedman H. Tumor necrosis factor induction by Candida albicans from human natural killer cells and monocytes. J Immunol. 1988 Dec 1;141(11):4047–4052. [PubMed] [Google Scholar]
  10. Garner R. E., Rubanowice K., Sawyer R. T., Hudson J. A. Secretion of TNF-alpha by alveolar macrophages in response to Candida albicans mannan. J Leukoc Biol. 1994 Feb;55(2):161–168. doi: 10.1002/jlb.55.2.161. [DOI] [PubMed] [Google Scholar]
  11. Goldman D., Lee S. C., Casadevall A. Pathogenesis of pulmonary Cryptococcus neoformans infection in the rat. Infect Immun. 1994 Nov;62(11):4755–4761. doi: 10.1128/iai.62.11.4755-4761.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gomez M. J., Torosantucci A., Quinti I., Testa U., Peschle C., Cassone A. Mannoprotein-induced anti-U937 cell cytotoxicity in peripheral blood mononuclear cells from uninfected or HIV-infected subjects: role of interferon-gamma and tumor necrosis factor-alpha. Cell Immunol. 1993 Dec;152(2):530–543. doi: 10.1006/cimm.1993.1310. [DOI] [PubMed] [Google Scholar]
  13. Goren M. B., Warren J. Immunofluorescence studies of reactions at the Cryptococcal capsule. J Infect Dis. 1968 Apr;118(2):215–229. doi: 10.1093/infdis/118.2.215. [DOI] [PubMed] [Google Scholar]
  14. Houpt D. C., Pfrommer G. S., Young B. J., Larson T. A., Kozel T. R. Occurrences, immunoglobulin classes, and biological activities of antibodies in normal human serum that are reactive with Cryptococcus neoformans glucuronoxylomannan. Infect Immun. 1994 Jul;62(7):2857–2864. doi: 10.1128/iai.62.7.2857-2864.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. James P. G., Cherniak R. Galactoxylomannans of Cryptococcus neoformans. Infect Immun. 1992 Mar;60(3):1084–1088. doi: 10.1128/iai.60.3.1084-1088.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jouault T., Bernigaud A., Lepage G., Trinel P. A., Poulain D. The Candida albicans phospholipomannan induces in vitro production of tumour necrosis factor-alpha from human and murine macrophages. Immunology. 1994 Oct;83(2):268–273. [PMC free article] [PubMed] [Google Scholar]
  17. Keller R. G., Pfrommer G. S., Kozel T. R. Occurrences, specificities, and functions of ubiquitous antibodies in human serum that are reactive with the Cryptococcus neoformans cell wall. Infect Immun. 1994 Jan;62(1):215–220. doi: 10.1128/iai.62.1.215-220.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kozel T. R., Highison B., Stratton C. J. Localization on encapsulated Cryptococcus neoformans of serum components opsonic for phagocytosis by macrophages and neutrophils. Infect Immun. 1984 Feb;43(2):574–579. doi: 10.1128/iai.43.2.574-579.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kozel T. R. Non-encapsulated variant of Cryptococcus neoformans. II. Surface receptors for cryptococcal polysaccharide and their role in inhibition of phagocytosis by polysaccharide. Infect Immun. 1977 Apr;16(1):99–106. doi: 10.1128/iai.16.1.99-106.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kozel T. R. Opsonization and phagocytosis of Cryptococcus neoformans. Arch Med Res. 1993 Autumn;24(3):211–218. [PubMed] [Google Scholar]
  21. Levitz S. M., Dupont M. P., Smail E. H. Direct activity of human T lymphocytes and natural killer cells against Cryptococcus neoformans. Infect Immun. 1994 Jan;62(1):194–202. doi: 10.1128/iai.62.1.194-202.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Levitz S. M., Tabuni A., Kornfeld H., Reardon C. C., Golenbock D. T. Production of tumor necrosis factor alpha in human leukocytes stimulated by Cryptococcus neoformans. Infect Immun. 1994 May;62(5):1975–1981. doi: 10.1128/iai.62.5.1975-1981.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Levitz S. M. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev Infect Dis. 1991 Nov-Dec;13(6):1163–1169. doi: 10.1093/clinids/13.6.1163. [DOI] [PubMed] [Google Scholar]
  24. Mattsson E., Rollof J., Verhoef J., Van Dijk H., Fleer A. Serum-induced potentiation of tumor necrosis factor alpha production by human monocytes in response to staphylococcal peptidoglycan: involvement of different serum factors. Infect Immun. 1994 Sep;62(9):3837–3843. doi: 10.1128/iai.62.9.3837-3843.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McGaw T. G., Kozel T. R. Opsonization of Cryptococcus neoformans by human immunoglobulin G: masking of immunoglobulin G by cryptococcal polysaccharide. Infect Immun. 1979 Jul;25(1):262–267. doi: 10.1128/iai.25.1.262-267.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Murphy J. W. Cytokine profiles associated with induction of the anticryptococcal cell-mediated immune response. Infect Immun. 1993 Nov;61(11):4750–4759. doi: 10.1128/iai.61.11.4750-4759.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Murphy J. W., Hidore M. R., Wong S. C. Direct interactions of human lymphocytes with the yeast-like organism, Cryptococcus neoformans. J Clin Invest. 1993 Apr;91(4):1553–1566. doi: 10.1172/JCI116361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Murphy J. W., Mosley R. L., Cherniak R., Reyes G. H., Kozel T. R., Reiss E. Serological, electrophoretic, and biological properties of Cryptococcus neoformans antigens. Infect Immun. 1988 Feb;56(2):424–431. doi: 10.1128/iai.56.2.424-431.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Orendi J. M., Nottet H. S., Visser M. R., Verheul A. F., Snippe H., Verhoef J. Enhancement of HIV-1 replication in peripheral blood mononuclear cells by Cryptococcus neoformans is monocyte-dependent but tumour necrosis factor-independent. AIDS. 1994 Apr;8(4):423–429. doi: 10.1097/00002030-199404000-00003. [DOI] [PubMed] [Google Scholar]
  30. Patterson T. F., Andriole V. T. Current concepts in cryptococcosis. Eur J Clin Microbiol Infect Dis. 1989 May;8(5):457–465. doi: 10.1007/BF01964060. [DOI] [PubMed] [Google Scholar]
  31. Peterson P. K., Gekker G., Chao C. C., Hu S. X., Edelman C., Balfour H. H., Jr, Verhoef J. Human cytomegalovirus-stimulated peripheral blood mononuclear cells induce HIV-1 replication via a tumor necrosis factor-alpha-mediated mechanism. J Clin Invest. 1992 Feb;89(2):574–580. doi: 10.1172/JCI115623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pettoello-Mantovani M., Casadevall A., Kollmann T. R., Rubinstein A., Goldstein H. Enhancement of HIV-1 infection by the capsular polysaccharide of Cryptococcus neoformans. Lancet. 1992 Jan 4;339(8784):21–23. doi: 10.1016/0140-6736(92)90142-p. [DOI] [PubMed] [Google Scholar]
  33. Reiss E., Cherniak R., Eby R., Kaufman L. Enzyme immunoassay detection of IgM to galactoxylomannan of Cryptococcus neoformans. Diagn Immunol. 1984;2(2):109–115. [PubMed] [Google Scholar]
  34. Takashima T., Ohnishi K., Tsuyuguchi I., Kishimoto S. Differential regulation of formation of multinucleated giant cells from concanavalin A-stimulated human blood monocytes by IFN-gamma and IL-4. J Immunol. 1993 Apr 1;150(7):3002–3010. [PubMed] [Google Scholar]
  35. Timmerman C. P., Mattsson E., Martinez-Martinez L., De Graaf L., Van Strijp J. A., Verbrugh H. A., Verhoef J., Fleer A. Induction of release of tumor necrosis factor from human monocytes by staphylococci and staphylococcal peptidoglycans. Infect Immun. 1993 Oct;61(10):4167–4172. doi: 10.1128/iai.61.10.4167-4172.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Turner S. H., Cherniak R., Reiss E. Fractionation and characterization of galactoxylomannan from Cryptococcus neoformans. Carbohydr Res. 1984 Feb 15;125(2):343–349. doi: 10.1016/0008-6215(84)85172-1. [DOI] [PubMed] [Google Scholar]
  37. Turner S. H., Cherniak R., Reiss E., Kwon-Chung K. J. Structural variability in the glucuronoxylomannan of Cryptococcus neoformans serotype A isolates determined by 13C NMR spectroscopy. Carbohydr Res. 1992 Sep 2;233:205–218. doi: 10.1016/s0008-6215(00)90932-7. [DOI] [PubMed] [Google Scholar]
  38. Vecchiarelli A., Puliti M., Torosantucci A., Cassone A., Bistoni F. In vitro production of tumor necrosis factor by murine splenic macrophages stimulated with mannoprotein constituents of Candida albicans cell wall. Cell Immunol. 1991 Apr 15;134(1):65–76. doi: 10.1016/0008-8749(91)90331-5. [DOI] [PubMed] [Google Scholar]
  39. Vecchiarelli A., Retini C., Pietrella D., Monari C., Tascini C., Beccari T., Kozel T. R. Downregulation by cryptococcal polysaccharide of tumor necrosis factor alpha and interleukin-1 beta secretion from human monocytes. Infect Immun. 1995 Aug;63(8):2919–2923. doi: 10.1128/iai.63.8.2919-2923.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Weidemann B., Brade H., Rietschel E. T., Dziarski R., Bazil V., Kusumoto S., Flad H. D., Ulmer A. J. Soluble peptidoglycan-induced monokine production can be blocked by anti-CD14 monoclonal antibodies and by lipid A partial structures. Infect Immun. 1994 Nov;62(11):4709–4715. doi: 10.1128/iai.62.11.4709-4715.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Weinberg P. B., Becker S., Granger D. L., Koren H. S. Growth inhibition of Cryptococcus neoformans by human alveolar macrophages. Am Rev Respir Dis. 1987 Nov;136(5):1242–1247. doi: 10.1164/ajrccm/136.5.1242. [DOI] [PubMed] [Google Scholar]
  42. Wright S. D. Multiple receptors for endotoxin. Curr Opin Immunol. 1991 Feb;3(1):83–90. doi: 10.1016/0952-7915(91)90082-c. [DOI] [PubMed] [Google Scholar]
  43. Zhang Y., Doerfler M., Lee T. C., Guillemin B., Rom W. N. Mechanisms of stimulation of interleukin-1 beta and tumor necrosis factor-alpha by Mycobacterium tuberculosis components. J Clin Invest. 1993 May;91(5):2076–2083. doi: 10.1172/JCI116430. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES