1887

Abstract

The pathogenesis of infection has been studied extensively with respect to inflammatory and pathological changes, but very little information is available regarding the morphology of yeast cells during the course of infection. Electron microscopy of in murine pulmonary infection revealed increased cell wall thickness with time, but this difference was only partially accounted for by increases in cell diameter. Cell walls of melanized cells were thicker than those of nonmelanized cells 2 h after infection, and the cell wall of yeast became blacker with time, suggesting that melanization contributes to the increased cell wall thickness. Heterogeneous cell populations emerged, with the appearance of giant forms. While for ATCC strain 24067 (serotype D) the full spectrum of cell sizes were observed, for strains H99 (serotype A) and 3501 (serotype D) cells were divisible into two populations, giant and micro forms. In contrast to cellular heterogeneity, the epitope recognized by a protective mAb on the capsular glucuronoxylomannan (GXM) was found at all times of infection. Immunoelectron microscopy using mAbs to GXM demonstrated reactivity with intracellular structures, suggesting that synthesis of capsular polysaccharide occurs, at least in part, in the cytoplasm. In summary, the results indicate that: (i) the infection is dynamic with respect to yeast cell morphology; (ii) giant cell forms arise in tissue during the course of infection; (iii) cell walls blacken and thicken during the course of infection, consistent with melanin synthesis during infection; and (iv) GXM epitopes are found in the capsule, cell wall and cytoplasm, consistent with intracellular polysaccharide synthesis. The results indicate that the population of cells in tissue is in a highly dynamic state, implying that the immune system must confront cells with varying characteristics during the course of infection.

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2001-08-01
2019-12-13
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References

  1. Al-Doory, Y. ( 1971; ). The ultrastructure of Cryptococcus neoformans. Sabouraudia 9, 113-118.[CrossRef]
    [Google Scholar]
  2. Casadevall, A. & Perfect, J. R. (1998). Cryptococcus neoformans. Washington, DC: American Society for Microbiology.
  3. Casadevall, A., Cleare, W., Feldmesser, M. & 12 other authors ( 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.
    [Google Scholar]
  4. Cassone, A., Simonetti, N. & Strippoli, V. ( 1974; ). Wall structure and bud formation in Cryptococcus neoformans. Arch Microbiol 95, 205-212.[CrossRef]
    [Google Scholar]
  5. Chang, Y. C., Penoyer, L. A. & Kwon-Chung, K. J. ( 1996; ). The second capsule gene of Cryptococcus neoformans, CAP64, is essential for virulence. Infect Immun 64, 1977-1983.
    [Google Scholar]
  6. Cruickshank, J. G., Cavill, R. & Jelbert, M. ( 1973; ). Cryptococcus neoformans of unusual morphology. Appl Microbiol 25, 309-312.
    [Google Scholar]
  7. Currie, B. P. & Casadevall, A. ( 1994; ). Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New York City. Clin Infect Dis 19, 1029-1033.[CrossRef]
    [Google Scholar]
  8. Doering, T. L. ( 1999; ). A unique alpha-1,3 mannosyltransferase of the pathogenic fungus Cryptococcus neoformans. J Bacteriol 181, 5482-5488.
    [Google Scholar]
  9. Doering, T. L. ( 2000; ). How does Cryptococcus get its coat? Trends Microbiol 8, 547-553.[CrossRef]
    [Google Scholar]
  10. Feldmesser, M. & Casadevall, A. ( 1997; ). Effect of serum IgG1 to Cryptococcus neoformans glucuronoxylomannan on murine pulmonary infection. J Immunol 158, 790-799.
    [Google Scholar]
  11. Feldmesser, M., Casadevall, A., Kress, Y., Spira, G. & Orlofsky, A. ( 1997; ). Eosinophil-Cryptococcus neoformans interactions in vivo and in vitro. Infect Immun 65, 1899-1907.
    [Google Scholar]
  12. Feldmesser, M., Kress, Y. & Casadevall, A. ( 1998; ). Effect of antibody to capsular polysaccharide on eosinophilic pneumonia in murine infection with Cryptococcus neoformans. J Infect Dis 177, 1639-1646.[CrossRef]
    [Google Scholar]
  13. Feldmesser, M., Kress, Y., Novikoff, P. & Casadevall, A. ( 2000a; ). Cryptococcus neoformans is a facultative intracellular pathogen in murine pulmonary infection. Infect Immun 68, 4225-4237.[CrossRef]
    [Google Scholar]
  14. Feldmesser, M., Rivera, J., Kress, Y. & Casadevall, A. ( 2000b; ). Antibody interactions with the capsule of Cryptococcus neoformans. Infect Immun 68, 3642-3650.[CrossRef]
    [Google Scholar]
  15. Franzot, S. P., Salkin, I. F. & Casadevall, A. ( 1999; ). Cryptococcus neoformans var. grubii: separate varietal status for Cryptococcus neoformans serotype A isolates. J Clin Microbiol 37, 838-840.
    [Google Scholar]
  16. Fries, B. C., Goldman, D. L., Cherniak, R., Ju, R. & Casadevall, A. ( 1999; ). Phenotypic switching in Cryptococcus neoformans results in changes in cellular morphology and glucuronoxylomannan structure. Infect Immun 67, 6076-6083.
    [Google Scholar]
  17. Fromtling, R. A., Shadomy, H. J. & Jacobson, E. S. ( 1982; ). Decreased virulence in stable, acapsular mutants of Cryptococcus neoformans. Mycopathologia 79, 23-29.[CrossRef]
    [Google Scholar]
  18. Goldman, D. L., Fries, B. C., Franzot, S. P., Montella, L. & Casadevall, A. ( 1998; ). Phenotypic switching in the human pathogenic fungus Cryptococcus neoformans is associated with changes in virulence and pulmonary inflammatory response in rodents. Proc Natl Acad Sci USA 95, 14967-14972.[CrossRef]
    [Google Scholar]
  19. Jacobson, E. S. & Tingler, M. J. ( 1994; ). Strains of Cryptococcus neoformans with defined capsular phenotypes. J Med Vet Mycol 32, 401-404.[CrossRef]
    [Google Scholar]
  20. Jacobson, E. S., Ayers, D. J., Harrell, A. C. & Nicholas, C. C. ( 1982; ). Genetic and phenotypic characterization of capsule mutants of Cryptococcus neoformans. J Bacteriol 150, 1292-1296.
    [Google Scholar]
  21. Levitz, S. M. ( 1991; ). The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev Infect Dis 13, 1163-1169.[CrossRef]
    [Google Scholar]
  22. Liu, L., Wakamatsu, K., Ito, S. & Williamson, P. R. ( 1999; ). Catecholamine oxidative products, but not melanin, are produced by Cryptococcus neoformans during neuropathogenesis in mice. Infect Immun 67, 108-112.
    [Google Scholar]
  23. Love, G. L., Boyd, G. D. & Greer, D. L. ( 1985; ). Large Cryptococcus neoformans isolated from brain abscess. J Clin Microbiol 22, 1068-1070.
    [Google Scholar]
  24. Mitchell, T. G. & Perfect, J. R. ( 1995; ). Cryptococcosis in the era of AIDS – 100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev 8, 515-548.
    [Google Scholar]
  25. Mochizuki, T., Tanaka, S. & Watanabe, S. ( 1987; ). Ultrastructure of the mitotic apparatus in Cryptococcus neoformans. J Med Vet Mycol 25, 223-233.[CrossRef]
    [Google Scholar]
  26. Mukherjee, J., Casadevall, A. & Scharff, M. D. ( 1993; ). Molecular characterization of the humoral responses to Cryptococcus neoformans infection and glucuronoxylomannan-tetanus toxoid conjugate immunization. J Exp Med 177, 1105-1116.[CrossRef]
    [Google Scholar]
  27. Mukherjee, J., Nussbaum, G., Scharff, M. D. & Casadevall, A. ( 1995; ). Protective and nonprotective monoclonal antibodies to Cryptococcus neoformans originating from one B cell. J Exp Med 181, 405-409.[CrossRef]
    [Google Scholar]
  28. Nosanchuk, J. D., Valadon, P., Feldmesser, M. & Casadevall, A. ( 1999; ). Melanization of Cryptococcus neoformans in murine infection. Mol Cell Biol 19, 745-750.
    [Google Scholar]
  29. Restrepo, A. ( 2000; ). Morphological aspects of Paracoccidioides brasiliensis in lymph nodes: implications for the prolonged latency of paracoccidioidomycosis? Med Mycol 38, 317-322.[CrossRef]
    [Google Scholar]
  30. Sakaguchi, N., Baba, T., Fukuzawa, M. & Ohno, S. ( 1993; ). Ultrastructural study of Cryptococcus neoformans by quick-freezing and deep-etching method. Mycopathologia 121, 133-141.[CrossRef]
    [Google Scholar]
  31. Small, J. M., Mitchell, T. G. & Wheat, R. W. ( 1986; ). Strain variation in composition and molecular size of the capsular polysaccharide of Cryptococcus neoformans serotype A. Infect Immun 54, 735-741.
    [Google Scholar]
  32. Spiropulu, C., Eppard, R. A., Otteson, E. & Kozel, T. R. ( 1989; ). Antigenic variation within serotypes of Cryptococcus neoformans detected by monoclonal antibodies specific for the capsular polysaccharide. Infect Immun 57, 3240-3242.
    [Google Scholar]
  33. Sweany, H. C., Gorelick, D., Coller, F. C. & Jones, J. L. ( 1962; ). Pathology and some diagnostic features of histoplasmosis in patients entering a Missouri hospital. The ′B′ group. Dis Chest 42, 128-150.[CrossRef]
    [Google Scholar]
  34. Takeo, K., Uesaka, I., Uehira, K. & Nishimura, M. ( 1973; ). Fine structure of Cryptococcus neoformans grown in vivo as observed by freeze-etching. J Bacteriol 113, 1449-1454.
    [Google Scholar]
  35. Thammana, P. & Scharff, M. D. ( 1983; ). Immunoglobulin heavy chain class switch from IgM to IgG in a hybridoma. Eur J Immunol 13, 614-619.[CrossRef]
    [Google Scholar]
  36. Wang, Y. & Casadevall, A. ( 1994; ). Susceptibility of melanized and nonmelanized Cryptococcus neoformans to nitrogen- and oxygen-derived oxidants. Infect Immun 62, 3004-3007.
    [Google Scholar]
  37. Zuger, A., Louie, E., Holzman, R. S., Simberkoff, M. S. & Rahal, J. J. ( 1986; ). Cryptococcal disease in patients with the acquired immunodeficiency syndrome. Ann Intern Med 104, 234-240.[CrossRef]
    [Google Scholar]
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