Abstract
During infection, Cryptococcus neoformans capsular glucuronoxylomannan (GXM) is released into tissues, where it may be associated with a variety of deleterious immunological effects. Relatively little is known about the organ distribution and cellular localization of GXM antigen. Intravenous administration of GXM to rats resulted in persistent serum levels which declined with a half-life of 14.3 h in the first 74 h and 3 h thereafter, coincident with the appearance of serum antibodies to GXM. GXM was sequestered primarily in spleen tissue, with localization to marginal zone and follicular cells. Administration of the murine immunoglobulin G1 monoclonal antibody (MAb) 2H1 resulted in > 99% reduction in serum GXM level within 3 h. MAb 2H1 administration resulted in liver GXM deposition, with cellular localization primarily to Kupffer cells. GXM was also found in the spleens of MAb 2H1-treated rats, with localization to the marginal zones and follicles. Endotracheal administration of GXM resulted in low serum levels, with lung tissue having the highest GXM organ levels, localized primarily to alveolar macrophages. The results indicate that (i) intravenous administration to rats produced persistent serum GXM levels with a half-life similar to that found in mice and rabbits; (ii) endotracheal administration of GXM resulted in low serum levels; (iii) in the absence of specific antibody, GXM organ deposition occurs primarily in the spleen and is localized primarily to marginal zone macrophages; (iv) in the presence of specific immunoglobulin G1 antibody, GXM organ deposition occurs primarily in the liver and is localized primarily to Kupffer cells; and (vi) reticuloendothelial cells sequester GXM in the presence and absence of specific antibody.
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- BENNETT J. E., HASENCLEVER H. F. CRYPTOCOCCUS NEOFORMANS POLYSACCHARIDE: STUDIES OF SEROLOGIC PROPERTIES AND ROLE IN INFECTION. J Immunol. 1965 Jun;94:916–920. [PubMed] [Google Scholar]
- BLOOMFIELD N., GORDON M. A., ELMENDORF D. F., Jr DETECTION OF CRYPTOCOCCUS NEOFORMANS ANTIGEN IN BODY FLUIDS BY LATEX PARTICLE AGGLUTINATION. Proc Soc Exp Biol Med. 1963 Oct;114:64–67. doi: 10.3181/00379727-114-28586. [DOI] [PubMed] [Google Scholar]
- Bolaños B., Mitchell T. G. Phagocytosis and killing of Cryptococcus neoformans by rat alveolar macrophages in the absence of serum. J Leukoc Biol. 1989 Dec;46(6):521–528. doi: 10.1002/jlb.46.6.521. [DOI] [PubMed] [Google Scholar]
- Bulmer G. S., Sans M. D., Gunn C. M. Cryptococcus neoformans. I. Nonencapsulated mutants. J Bacteriol. 1967 Nov;94(5):1475–1479. doi: 10.1128/jb.94.5.1475-1479.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Casadevall A., Mukherjee J., Devi S. J., Schneerson R., Robbins J. B., Scharff M. D. Antibodies elicited by a Cryptococcus neoformans-tetanus toxoid conjugate vaccine have the same specificity as those elicited in infection. J Infect Dis. 1992 Jun;165(6):1086–1093. doi: 10.1093/infdis/165.6.1086. [DOI] [PubMed] [Google Scholar]
- Casadevall A., Mukherjee J., Scharff M. D. Monoclonal antibody based ELISAs for cryptococcal polysaccharide. J Immunol Methods. 1992 Sep 18;154(1):27–35. doi: 10.1016/0022-1759(92)90209-c. [DOI] [PubMed] [Google Scholar]
- Casadevall A., Scharff M. D. The mouse antibody response to infection with Cryptococcus neoformans: VH and VL usage in polysaccharide binding antibodies. J Exp Med. 1991 Jul 1;174(1):151–160. doi: 10.1084/jem.174.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- DROUHET E., SEGRETAIN G. Inhibition de la migration leucocytaire in vitro par un polyoside capsulaire de Torulopsis (Cryptococcus) neoformans. Ann Inst Pasteur (Paris) 1951 Dec;81(6):674–676. [PubMed] [Google Scholar]
- Diamond R. D., Bennett J. E. Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann Intern Med. 1974 Feb;80(2):176–181. doi: 10.7326/0003-4819-80-2-176. [DOI] [PubMed] [Google Scholar]
- Dong Z. M., Murphy J. W. Intravascular cryptococcal culture filtrate (CneF) and its major component, glucuronoxylomannan, are potent inhibitors of leukocyte accumulation. Infect Immun. 1995 Mar;63(3):770–778. doi: 10.1128/iai.63.3.770-778.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dromer F., Salamero J., Contrepois A., Carbon C., Yeni P. Production, characterization, and antibody specificity of a mouse monoclonal antibody reactive with Cryptococcus neoformans capsular polysaccharide. Infect Immun. 1987 Mar;55(3):742–748. doi: 10.1128/iai.55.3.742-748.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Henderson D. K., Bennett J. E., Huber M. A. Long-lasting, specific immunologic unresponsiveness associated with cryptococcal meningitis. J Clin Invest. 1982 May;69(5):1185–1190. doi: 10.1172/JCI110555. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henderson D. K., Kan V. L., Bennett J. E. Tolerance to cryptococcal polysaccharide in cured cryptococcosis patients: failure of antibody secretion in vitro. Clin Exp Immunol. 1986 Sep;65(3):639–646. [PMC free article] [PubMed] [Google Scholar]
- Humphrey J. H. Tolerogenic or immunogenic activity of hapten-conjugated polysaccharides correlated with cellular localization. Eur J Immunol. 1981 Mar;11(3):212–220. doi: 10.1002/eji.1830110310. [DOI] [PubMed] [Google Scholar]
- Kappe R., Müller J. Rapid clearance of Candida albicans mannan antigens by liver and spleen in contrast to prolonged circulation of Cryptococcus neoformans antigens. J Clin Microbiol. 1991 Aug;29(8):1665–1669. doi: 10.1128/jcm.29.8.1665-1669.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kozel T. R., Gotschlich E. C. The capsule of cryptococcus neoformans passively inhibits phagocytosis of the yeast by macrophages. J Immunol. 1982 Oct;129(4):1675–1680. [PubMed] [Google Scholar]
- Kozel T. R., Gulley W. F., Cazin J., Jr Immune response to Cryptococcus neoformans soluble polysaccharide: immunological unresponsiveness. Infect Immun. 1977 Dec;18(3):701–707. doi: 10.1128/iai.18.3.701-707.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kozel T. R., Pfrommer G. S., Guerlain A. S., Highison B. A., Highison G. J. Role of the capsule in phagocytosis of Cryptococcus neoformans. Rev Infect Dis. 1988 Jul-Aug;10 (Suppl 2):S436–S439. doi: 10.1093/cid/10.supplement_2.s436. [DOI] [PubMed] [Google Scholar]
- Kraal G., Ter Hart H., Meelhuizen C., Venneker G., Claassen E. Marginal zone macrophages and their role in the immune response against T-independent type 2 antigens: modulation of the cells with specific antibody. Eur J Immunol. 1989 Apr;19(4):675–680. doi: 10.1002/eji.1830190416. [DOI] [PubMed] [Google Scholar]
- Kwon-Chung K. J., Rhodes J. C. Encapsulation and melanin formation as indicators of virulence in Cryptococcus neoformans. Infect Immun. 1986 Jan;51(1):218–223. doi: 10.1128/iai.51.1.218-223.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mody C. H., Syme R. M. Effect of polysaccharide capsule and methods of preparation on human lymphocyte proliferation in response to Cryptococcus neoformans. Infect Immun. 1993 Feb;61(2):464–469. doi: 10.1128/iai.61.2.464-469.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mosley R. L., Murphy J. W., Cox R. A. Immunoadsorption of Cryptococcus-specific suppressor T-cell factors. Infect Immun. 1986 Mar;51(3):844–850. doi: 10.1128/iai.51.3.844-850.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muchmore H. G., Scott E. N., Felton F. G., Fromtling R. A. Cryptococcal capsular polysaccharide clearance in nonimmune mice. Mycopathologia. 1982 Apr 23;78(1):41–45. doi: 10.1007/BF00436580. [DOI] [PubMed] [Google Scholar]
- Mukherjee J., Scharff M. D., Casadevall A. Protective murine monoclonal antibodies to Cryptococcus neoformans. Infect Immun. 1992 Nov;60(11):4534–4541. doi: 10.1128/iai.60.11.4534-4541.1992. [DOI] [PMC free article] [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]
- Murphy J. W., Cox R. A. Induction of antigen-specific suppression by circulating Cryptococcus neoformans antigen. Clin Exp Immunol. 1988 Aug;73(2):174–180. [PMC free article] [PubMed] [Google Scholar]
- Murphy J. W., Cozad G. C. Immunological unresponsiveness induced by cryptococcal capsular polysaccharide assayed by the hemolytic plaque technique. Infect Immun. 1972 Jun;5(6):896–901. doi: 10.1128/iai.5.6.896-901.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Pettoello-Mantovani M., Casadevall A., Smarnworawong P., Goldstein H. Enhancement of HIV type 1 infectivity in vitro by capsular polysaccharide of Cryptococcus neoformans and Haemophilus influenzae. AIDS Res Hum Retroviruses. 1994 Sep;10(9):1079–1087. doi: 10.1089/aid.1994.10.1079. [DOI] [PubMed] [Google Scholar]
- Powderly W. G. Therapy for cryptococcal meningitis in patients with AIDS. Clin Infect Dis. 1992 Mar;14 (Suppl 1):S54–S59. doi: 10.1093/clinids/14.supplement_1.s54. [DOI] [PubMed] [Google Scholar]
- Russell M. W., Brown T. A., Claflin J. L., Schroer K., Mestecky J. Immunoglobulin A-mediated hepatobiliary transport constitutes a natural pathway for disposing of bacterial antigens. Infect Immun. 1983 Dec;42(3):1041–1048. doi: 10.1128/iai.42.3.1041-1048.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sundstrom J. B., Cherniak R. T-cell-dependent and T-cell-independent mechanisms of tolerance to glucuronoxylomannan of Cryptococcus neoformans serotype A. Infect Immun. 1993 Apr;61(4):1340–1345. doi: 10.1128/iai.61.4.1340-1345.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sundstrom J. B., Cherniak R. The glucuronoxylomannan of Cryptococcus neoformans serotype A is a type 2 T-cell-independent antigen. Infect Immun. 1992 Oct;60(10):4080–4087. doi: 10.1128/iai.60.10.4080-4087.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang D., Wells S. M., Stall A. M., Kabat E. A. Reaction of germinal centers in the T-cell-independent response to the bacterial polysaccharide alpha(1-->6)dextran. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2502–2506. doi: 10.1073/pnas.91.7.2502. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Rooijen N., Claassen E., Kraal G., Dijkstra C. D. Cytological basis of immune functions of the spleen. Immunocytochemical characterization of lymphoid and non-lymphoid cells involved in the 'in situ' immune response. Prog Histochem Cytochem. 1989;19(3):1–71. [PubMed] [Google Scholar]