Abstract
The dermotropism of Cryptococcus neoformans SLHA in congenitally athymic (nu/nu) and doubly immunodeficient beige-athymic (bg/bg-nu/nu) mice is described. Both bg/bg-nu/nu and nu/nu mice developed cutaneous cryptococcosis within 7 to 12 days following intravenous challenge with 10(4) encapsulated yeast cells. Macroscopically, cutaneous lesions appeared as small subcutaneous nodules without ulceration. Cryptococcal skin lesions were observed primarily on the flank of nu/nu mice, whereas skin lesions in bg/bg-nu/nu mice were distributed over the trunk, abdomen, and face. While bg/bg-nu/nu mice had four times as many macroscopic skin lesions as nu/nu mice on day 14 after intravenous challenge, the skin lesions in nu/nu mice were larger. Histopathology revealed large foci of encapsulated yeasts extending from the basement membrane of the epidermis through the dermis to the underlying musculature. Yeasts in these lesions evoked a minimal inflammatory response that consisted primarily of macrophages. Interestingly, yeast cells appeared to be degrading collagen bundles located in the dermis. The dermotropic strain used in this study produced gelatinase and other proteases in vitro. These results indicate that C. neoformans can be dermotropic in a T-cell-deficient host and that proteases may be a virulence factor(s).
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Balish E., Filutowicz H., Oberley T. D. Correlates of cell-mediated immunity in Candida albicans-colonized gnotobiotic mice. Infect Immun. 1990 Jan;58(1):107–113. doi: 10.1128/iai.58.1.107-113.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bartizal K. F., Salkowski C., Pleasants J. R., Balish E. The effect of microbial flora, diet, and age on the tumoricidal activity of natural killer cells. J Leukoc Biol. 1984 Dec;36(6):739–750. doi: 10.1002/jlb.36.6.739. [DOI] [PubMed] [Google Scholar]
- Borton L. K., Wintroub B. U. Disseminated cryptococcosis presenting as herpetiform lesions in a homosexual man with acquired immunodeficiency syndrome. J Am Acad Dermatol. 1984 Feb;10(2 Pt 2):387–390. doi: 10.1016/s0190-9622(84)80013-4. [DOI] [PubMed] [Google Scholar]
- Brueske C. H. Proteolytic activity of a clinical isolate of Cryptococcus neoformans. J Clin Microbiol. 1986 Mar;23(3):631–633. doi: 10.1128/jcm.23.3.631-633.1986. [DOI] [PMC free article] [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]
- Cauley L. K., Murphy J. W. Response of congenitally athymic (nude) and phenotypically normal mice to Cryptococcus neoformans infection. Infect Immun. 1979 Mar;23(3):644–651. doi: 10.1128/iai.23.3.644-651.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chu A. C., Hay R. J., MacDonald D. M. Cutaneous cryptococcosis. Br J Dermatol. 1980 Jul;103(1):95–100. doi: 10.1111/j.1365-2133.1980.tb15844.x. [DOI] [PubMed] [Google Scholar]
- Dixon D. M., Polak A. In vivo and in vitro studies with an atypical, rhinotropic isolate of Cryptococcus neoformans. Mycopathologia. 1986 Oct;96(1):33–40. doi: 10.1007/BF00467683. [DOI] [PubMed] [Google Scholar]
- Dykstra M. A., Friedman L. Pathogenesis, lethality, and immunizing effect of experimental cutaneous cryptococcosis. Infect Immun. 1978 May;20(2):446–455. doi: 10.1128/iai.20.2.446-455.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fromtling R. A., Abruzzo G. K., Ruiz A. Cryptococcus neoformans: a central nervous system isolate from an AIDS patient that is rhinotropic in a normal mouse model. Mycopathologia. 1988 May;102(2):79–86. doi: 10.1007/BF00437444. [DOI] [PubMed] [Google Scholar]
- Goldfarb R. H., Liotta L. A. Proteolytic enzymes in cancer invasion and metastasis. Semin Thromb Hemost. 1986 Oct;12(4):294–307. doi: 10.1055/s-2007-1003570. [DOI] [PubMed] [Google Scholar]
- Graybill J. R., Drutz D. J. Host defense in cryptococcosis. II. Cryptococcosis in the nude mouse. Cell Immunol. 1978 Oct;40(2):263–274. doi: 10.1016/0008-8749(78)90334-9. [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]
- Marquis G., Montplaisir S., Pelletier M., Mousseau S., Auger P. Genetic resistance to murine cryptococcosis: increased susceptibility in the CBA/N XID mutant strain of mice. Infect Immun. 1985 Jan;47(1):282–287. doi: 10.1128/iai.47.1.282-287.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matrisian L. M. Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet. 1990 Apr;6(4):121–125. doi: 10.1016/0168-9525(90)90126-q. [DOI] [PubMed] [Google Scholar]
- Moser S. A., Lyon F. L., Domer J. E., Williams J. E. Immunization of mice by intracutaneous inoculation with viable virulent Cryptococcus neoformans: immunological and histopathological parameters. Infect Immun. 1982 Feb;35(2):685–696. doi: 10.1128/iai.35.2.685-696.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müller H. E., Sethi K. K. Proteolytic activity of Cryptococcus neoformans against human plasma proteins. Med Microbiol Immunol. 1972;158(2):129–134. doi: 10.1007/BF02120478. [DOI] [PubMed] [Google Scholar]
- Nishimura K., Miyaji M. Histopathological studies on experimental cryptococcosis in nude mice. Mycopathologia. 1979 Sep 28;68(3):145–153. doi: 10.1007/BF00578522. [DOI] [PubMed] [Google Scholar]
- Ray T. L., Payne C. D. Comparative production and rapid purification of Candida acid proteinase from protein-supplemented cultures. Infect Immun. 1990 Feb;58(2):508–514. doi: 10.1128/iai.58.2.508-514.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rhodes J. C., Polacheck I., Kwon-Chung K. J. Phenoloxidase activity and virulence in isogenic strains of Cryptococcus neoformans. Infect Immun. 1982 Jun;36(3):1175–1184. doi: 10.1128/iai.36.3.1175-1184.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rico M. J., Penneys N. S. Cutaneous cryptococcosis resembling molluscum contagiosum in a patient with AIDS. Arch Dermatol. 1985 Jul;121(7):901–902. [PubMed] [Google Scholar]
- Salkowski C. A., Balish E. Inflammatory responses to cryptococcosis in congenitally athymic mice. J Leukoc Biol. 1991 Jun;49(6):533–541. doi: 10.1002/jlb.49.6.533. [DOI] [PubMed] [Google Scholar]
- Salkowski C. A., Balish E. Pathogenesis of Cryptococcus neoformans in congenitally immunodeficient beige athymic mice. Infect Immun. 1990 Oct;58(10):3300–3306. doi: 10.1128/iai.58.10.3300-3306.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sarosi G. A., Silberfarb P. M., Tosh F. E. Cutaneous cryptococcosis. A sentinel of disseminated disease. Arch Dermatol. 1971 Jul;104(1):1–3. doi: 10.1001/archderm.104.1.1. [DOI] [PubMed] [Google Scholar]
- Schupbach C. W., Wheeler C. E., Jr, Briggaman R. A., Warner N. A., Kanof E. P. Cutaneous manifestations of disseminated cryptococcosis. Arch Dermatol. 1976 Dec;112(12):1734–1740. [PubMed] [Google Scholar]
- Song M. M. Experimental cryptococcosis of the skin. Sabouraudia. 1974 Jul;12(2):133–137. doi: 10.1080/00362177485380191. [DOI] [PubMed] [Google Scholar]
- Thorgeirsson U. P., Turpeenniemi-Hujanen T., Williams J. E., Westin E. H., Heilman C. A., Talmadge J. E., Liotta L. A. NIH/3T3 cells transfected with human tumor DNA containing activated ras oncogenes express the metastatic phenotype in nude mice. Mol Cell Biol. 1985 Jan;5(1):259–262. doi: 10.1128/mcb.5.1.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ura H., Bonfil R. D., Reich R., Reddel R., Pfeifer A., Harris C. C., Klein-Szanto A. J. Expression of type IV collagenase and procollagen genes and its correlation with the tumorigenic, invasive, and metastatic abilities of oncogene-transformed human bronchial epithelial cells. Cancer Res. 1989 Aug 15;49(16):4615–4621. [PubMed] [Google Scholar]
- Van Cutsem J., Fransen J., Van Gerven F., Janssen P. A. Experimental cryptococcosis: dissemination of Cryptococcus neoformans and dermotropism in guinea-pigs. Mykosen. 1986 Dec;29(12):561–575. [PubMed] [Google Scholar]