Abstract
We previously showed that surface mannans of Candida albicans function as adhesins during yeast cell attachment to mouse splenic marginal zone macrophages. The mannan adhesin fraction was encapsulated into liposomes and used to vaccinate mice over a 5- to 6-week period. Circulating agglutinins specific for the fraction correlated with increased resistance to disseminated candidiasis. Antiserum from vaccinated animals protected naive BALB/cByJ mice against C. albicans serotype A and B strains and Candida tropicalis. Antiserum also protected SCID mice against disseminated disease. The serum protective ability was stable at 56 degrees C, but this ability was adsorbed by C. albicans cells. The antiserum was divided into three fractions after separation by high-performance liquid chromatography. One fraction contained all of the agglutinin activity and transferred resistance to naive mice. A second fraction also transferred resistance. Two monoclonal antibodies (MAbs) specific for candidal surface determinants were obtained. MAb B6.1 is specific for a mannan epitope in the adhesin fraction, and MAb B6 is specific for a different epitope in the fraction. Both MAbs are immunoglobulin M, and both strongly agglutinate candidal cells, but only MAb B6.1 protected both normal and SCID mice against disseminated candidiasis. In one experiment, 10 normal mice were given MAb B6.1 and challenged with yeast cells. Six mice survived the 67-day observation period; 4 of the survivors were cured as evidenced by the lack of CFU in the kidney and spleen. Our studies show that antibodies against certain cell surface antigens of C. albicans help the host resist disseminated candidiasis.
Full Text
The Full Text of this article is available as a PDF (195.0 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anttila V. J., Ruutu P., Bondestam S., Jansson S. E., Nordling S., Färkkilä M., Sivonen A., Castren M., Ruutu T. Hepatosplenic yeast infection in patients with acute leukemia: a diagnostic problem. Clin Infect Dis. 1994 Jun;18(6):979–981. doi: 10.1093/clinids/18.6.979. [DOI] [PubMed] [Google Scholar]
- Banerjee U., Mohapatra L. N., Kumar R. Role of antibody in defence against murine candidosis. Indian J Med Res. 1984 Jun;79:760–765. [PubMed] [Google Scholar]
- Berenguer J., Buck M., Witebsky F., Stock F., Pizzo P. A., Walsh T. J. Lysis-centrifugation blood cultures in the detection of tissue-proven invasive candidiasis. Disseminated versus single-organ infection. Diagn Microbiol Infect Dis. 1993 Aug-Sep;17(2):103–109. doi: 10.1016/0732-8893(93)90020-8. [DOI] [PubMed] [Google Scholar]
- Brawner D. L., Cutler J. E. Cell surface and intracellular expression of two Candida albicans antigens during in vitro and in vivo growth. Microb Pathog. 1987 Apr;2(4):249–257. doi: 10.1016/0882-4010(87)90123-9. [DOI] [PubMed] [Google Scholar]
- Brawner D. L., Cutler J. E. Oral Candida albicans isolates from nonhospitalized normal carriers, immunocompetent hospitalized patients, and immunocompromised patients with or without acquired immunodeficiency syndrome. J Clin Microbiol. 1989 Jun;27(6):1335–1341. doi: 10.1128/jcm.27.6.1335-1341.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brawner D. L., Cutler J. E. Ultrastructural and biochemical studies of two dynamically expressed cell surface determinants on Candida albicans. Infect Immun. 1986 Jan;51(1):327–336. doi: 10.1128/iai.51.1.327-336.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brawner D. L., Cutler J. E. Variability in expression of a cell surface determinant on Candida albicans as evidenced by an agglutinating monoclonal antibody. Infect Immun. 1984 Mar;43(3):966–972. doi: 10.1128/iai.43.3.966-972.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brawner D. L., Cutler J. E. Variability in expression of cell surface antigens of Candida albicans during morphogenesis. Infect Immun. 1986 Jan;51(1):337–343. doi: 10.1128/iai.51.1.337-343.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Critchley I. A., Douglas L. J. Isolation and partial characterization of an adhesin from Candida albicans. J Gen Microbiol. 1987 Mar;133(3):629–636. doi: 10.1099/00221287-133-3-629. [DOI] [PubMed] [Google Scholar]
- Filler S. G., Ibe B. O., Ibrahim A. S., Ghannoum M. A., Raj J. U., Edwards J. E., Jr Mechanisms by which Candida albicans induces endothelial cell prostaglandin synthesis. Infect Immun. 1994 Mar;62(3):1064–1069. doi: 10.1128/iai.62.3.1064-1069.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fruit J., Cailliez J. C., Odds F. C., Poulain D. Expression of an epitope by surface glycoproteins of Candida albicans. Variability among species, strains and yeast cells of the genus Candida. J Med Vet Mycol. 1990;28(3):241–252. doi: 10.1080/02681219080000301. [DOI] [PubMed] [Google Scholar]
- Garner R. E., Domer J. E. Lack of effect of Candida albicans mannan on development of protective immune responses in experimental murine candidiasis. Infect Immun. 1994 Feb;62(2):738–741. doi: 10.1128/iai.62.2.738-741.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giger D. K., Domer J. E., Moser S. A., McQuitty J. T., Jr Experimental murine candidiasis: pathological and immune responses in T-lymphocyte-depleted mice. Infect Immun. 1978 Sep;21(3):729–737. doi: 10.1128/iai.21.3.729-737.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Han Y., van Rooijen N., Cutler J. E. Binding of Candida albicans yeast cells to mouse popliteal lymph node tissue is mediated by macrophages. Infect Immun. 1993 Aug;61(8):3244–3249. doi: 10.1128/iai.61.8.3244-3249.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hazen K. C., Brawner D. L., Riesselman M. H., Jutila M. A., Cutler J. E. Differential adherence of hydrophobic and hydrophilic Candida albicans yeast cells to mouse tissues. Infect Immun. 1991 Mar;59(3):907–912. doi: 10.1128/iai.59.3.907-912.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kanbe T., Cutler J. E. Evidence for adhesin activity in the acid-stable moiety of the phosphomannoprotein cell wall complex of Candida albicans. Infect Immun. 1994 May;62(5):1662–1668. doi: 10.1128/iai.62.5.1662-1668.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kanbe T., Han Y., Redgrave B., Riesselman M. H., Cutler J. E. Evidence that mannans of Candida albicans are responsible for adherence of yeast forms to spleen and lymph node tissue. Infect Immun. 1993 Jun;61(6):2578–2584. doi: 10.1128/iai.61.6.2578-2584.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kanbe T., Jutila M. A., Cutler J. E. Evidence that Candida albicans binds via a unique adhesion system on phagocytic cells in the marginal zone of the mouse spleen. Infect Immun. 1992 May;60(5):1972–1978. doi: 10.1128/iai.60.5.1972-1978.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kanbe T., Li R. K., Wadsworth E., Calderone R. A., Cutler J. E. Evidence for expression of the C3d receptor of Candida albicans in vitro and in vivo obtained by immunofluorescence and immunoelectron microscopy. Infect Immun. 1991 May;59(5):1832–1838. doi: 10.1128/iai.59.5.1832-1838.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kobayashi H., Shibata N., Nakada M., Chaki S., Mizugami K., Ohkubo Y., Suzuki S. Structural study of cell wall phosphomannan of Candida albicans NIH B-792 (serotype B) strain, with special reference to 1H and 13C NMR analyses of acid-labile oligomannosyl residues. Arch Biochem Biophys. 1990 Apr;278(1):195–204. doi: 10.1016/0003-9861(90)90248-w. [DOI] [PubMed] [Google Scholar]
- Komshian S. V., Uwaydah A. K., Sobel J. D., Crane L. R. Fungemia caused by Candida species and Torulopsis glabrata in the hospitalized patient: frequency, characteristics, and evaluation of factors influencing outcome. Rev Infect Dis. 1989 May-Jun;11(3):379–390. doi: 10.1093/clinids/11.3.379. [DOI] [PubMed] [Google Scholar]
- Laforce F. M., Mills D. M., Iverson K., Cousins R., Everett E. D. Inhibition of leukocyte candidacidal activity by serum from patients with disseminated candidiasis. J Lab Clin Med. 1975 Oct;86(4):657–666. [PubMed] [Google Scholar]
- Lehrer N., Segal E., Lis H., Gov Y. Effect of Candida albicans cell wall components on the adhesion of the fungus to human and murine vaginal mucosa. Mycopathologia. 1988 May;102(2):115–121. doi: 10.1007/BF00437448. [DOI] [PubMed] [Google Scholar]
- Li R. K., Cutler J. E. Chemical definition of an epitope/adhesin molecule on Candida albicans. J Biol Chem. 1993 Aug 25;268(24):18293–18299. [PubMed] [Google Scholar]
- MOURAD S., FRIEDMAN L. Active immunization of mice against Candida albicans. Proc Soc Exp Biol Med. 1961 Mar;106:570–572. doi: 10.3181/00379727-106-26405. [DOI] [PubMed] [Google Scholar]
- Martinez J. P., Gil M. L., Casanova M., Lopez-Ribot J. L., Garcia De Lomas J., Sentandreu R. Wall mannoproteins in cells from colonial phenotypic variants of Candida albicans. J Gen Microbiol. 1990 Dec;136(12):2421–2432. doi: 10.1099/00221287-136-12-2421. [DOI] [PubMed] [Google Scholar]
- Matthews R. C., Burnie J. P., Howat D., Rowland T., Walton F. Autoantibody to heat-shock protein 90 can mediate protection against systemic candidosis. Immunology. 1991 Sep;74(1):20–24. [PMC free article] [PubMed] [Google Scholar]
- Matthews R., Burnie J. Acquired immunity to systemic candidiasis in immunodeficient mice: role of antibody to heat-shock protein 90. J Infect Dis. 1992 Nov;166(5):1193–1195. doi: 10.1093/infdis/166.5.1193. [DOI] [PubMed] [Google Scholar]
- Meunier F., Aoun M., Bitar N. Candidemia in immunocompromised patients. Clin Infect Dis. 1992 Mar;14 (Suppl 1):S120–S125. doi: 10.1093/clinids/14.supplement_1.s120. [DOI] [PubMed] [Google Scholar]
- Miyakawa Y., Kuribayashi T., Kagaya K., Suzuki M., Nakase T., Fukazawa Y. Role of specific determinants in mannan of Candida albicans serotype A in adherence to human buccal epithelial cells. Infect Immun. 1992 Jun;60(6):2493–2499. doi: 10.1128/iai.60.6.2493-2499.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Molinari A., Gomez M. J., Crateri P., Torosantucci A., Cassone A., Arancia G. Differential cell surface expression of mannoprotein epitopes in yeast and mycelial forms of Candida albicans. Eur J Cell Biol. 1993 Feb;60(1):146–153. [PubMed] [Google Scholar]
- Mourad S., Friedman L. Passive immunization of mice against Candida albicans. Sabouraudia. 1968 Feb;6(2):103–105. [PubMed] [Google Scholar]
- Mukherjee J., Scharff M. D., Casadevall A. Cryptococcus neoformans infection can elicit protective antibodies in mice. Can J Microbiol. 1994 Oct;40(10):888–892. doi: 10.1139/m94-141. [DOI] [PubMed] [Google Scholar]
- Mukherjee J., Zuckier L. S., Scharff M. D., Casadevall A. Therapeutic efficacy of monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan alone and in combination with amphotericin B. Antimicrob Agents Chemother. 1994 Mar;38(3):580–587. doi: 10.1128/aac.38.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mukherjee S., Lee S., Mukherjee J., Scharff M. D., Casadevall A. Monoclonal antibodies to Cryptococcus neoformans capsular polysaccharide modify the course of intravenous infection in mice. Infect Immun. 1994 Mar;62(3):1079–1088. doi: 10.1128/iai.62.3.1079-1088.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pearsall N. N., Adams B. L., Bunni R. Immunologic responses to Candida albicans. III. Effects of passive transfer of lymphoid cells or serum on murine candidiasis. J Immunol. 1978 Apr;120(4):1176–1180. [PubMed] [Google Scholar]
- Qian Q., Jutila M. A., Van Rooijen N., Cutler J. E. Elimination of mouse splenic macrophages correlates with increased susceptibility to experimental disseminated candidiasis. J Immunol. 1994 May 15;152(10):5000–5008. [PubMed] [Google Scholar]
- Reboli A. C. Diagnosis of invasive candidiasis by a dot immunobinding assay for Candida antigen detection. J Clin Microbiol. 1993 Mar;31(3):518–523. doi: 10.1128/jcm.31.3.518-523.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schaberg D. R., Culver D. H., Gaynes R. P. Major trends in the microbial etiology of nosocomial infection. Am J Med. 1991 Sep 16;91(3B):72S–75S. doi: 10.1016/0002-9343(91)90346-y. [DOI] [PubMed] [Google Scholar]
- Sieck T. G., Moors M. A., Buckley H. R., Blank K. J. Protection against murine disseminated candidiasis mediated by a Candida albicans-specific T-cell line. Infect Immun. 1993 Aug;61(8):3540–3543. doi: 10.1128/iai.61.8.3540-3543.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tronchin G., Bouchara J. P., Annaix V., Robert R., Senet J. M. Fungal cell adhesion molecules in Candida albicans. Eur J Epidemiol. 1991 Jan;7(1):23–33. doi: 10.1007/BF00221338. [DOI] [PubMed] [Google Scholar]
- Walker S. M., Urbaniak S. J. A serum-dependent defect of neutrophil function in chronic mucocutaneous candidiasis. J Clin Pathol. 1980 Apr;33(4):370–372. doi: 10.1136/jcp.33.4.370. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whelan W. L., Delga J. M., Wadsworth E., Walsh T. J., Kwon-Chung K. J., Calderone R., Lipke P. N. Isolation and characterization of cell surface mutants of Candida albicans. Infect Immun. 1990 Jun;58(6):1552–1557. doi: 10.1128/iai.58.6.1552-1557.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]