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Experimental systemic infection with Cryptococcus neoformans var. grubii and Cryptococcus gattii in normal and immunodeficient mice.
Med Mycol. 2006 Nov; 44(7):601-10.MM

Abstract

Cryptococcus neoformans (Cn) var. grubii or Cryptococcus neoformans var. neoformans infection is usually associated with immunocompromised hosts, whereas Cryptococcusgattii more frequently causes disease in immunocompetent hosts. We examined the effects of immunodeficiency and glucocorticoid-induced immunosuppression on systemic murine infection induced by i.v. inoculation with these pathogens. SCID and immunocompetent BALB/c and C57BL/6 mice were infected with <or=107 yeast of Cn var. grubii or C. gattii; immunosuppressed BALB/c mice were infected with <or=106 yeast. Mortality was inoculum size-dependent in each model system, for both organisms. Following infection with 106 CFU of either Cn var. grubii or C. gattii immunocompetent BALB/c mice survived longer than immunosuppressed mice (P<0.0001 in both cases); no differences were found using lower inocula. SCID mice infected with Cn var. grubii or C. gattii died sooner than BALB/c mice (P<0.0013, all comparisons). Unexpectedly, BALB/c mice infected with C. gattii developed external lesions. Immunocompetent mice developed rectal prolapse more frequently whereas immunosuppressed mice developed more frequent skin lesions, predominantly on the tail. The fungal burden was especially high in rectum, skin and lung tissues. Histologic examination showed extensive infection of the rectum and skin and pneumonitis. Determination of CFU from various organs of immunocompetent BALB/c mice infected i.v. with 105 CFU of C. gattii or Cn var. grubii showed significant temporal increase of burdens of Cn var. grubii in brain and liver (P<0.003); other organs showed decreasing fungal burden. C.gattii was recovered only from liver and lungs, no CFU were detected in the other organs. As opposed to epidemiologic observations, our results demonstrate no predilection by C. gattii for infection of immunocompetent over immunosuppressed hosts; immunosuppression increased the risk of severe cryptococcosis by both varieties, especially at high inocula. This is the first report of C. gattii inducing experimental cutaneous and intestinal mucosal infection; Cn var. grubii did not affect these tissues, indicating differences in tissue tropism of these pathogens.

Authors+Show Affiliations

California Institute for Medical Research, San Jose, California, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17071553

Citation

Capilla, Javier, et al. "Experimental Systemic Infection With Cryptococcus Neoformans Var. Grubii and Cryptococcus Gattii in Normal and Immunodeficient Mice." Medical Mycology, vol. 44, no. 7, 2006, pp. 601-10.
Capilla J, Maffei CM, Clemons KV, et al. Experimental systemic infection with Cryptococcus neoformans var. grubii and Cryptococcus gattii in normal and immunodeficient mice. Med Mycol. 2006;44(7):601-10.
Capilla, J., Maffei, C. M., Clemons, K. V., Sobel, R. A., & Stevens, D. A. (2006). Experimental systemic infection with Cryptococcus neoformans var. grubii and Cryptococcus gattii in normal and immunodeficient mice. Medical Mycology, 44(7), 601-10.
Capilla J, et al. Experimental Systemic Infection With Cryptococcus Neoformans Var. Grubii and Cryptococcus Gattii in Normal and Immunodeficient Mice. Med Mycol. 2006;44(7):601-10. PubMed PMID: 17071553.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Experimental systemic infection with Cryptococcus neoformans var. grubii and Cryptococcus gattii in normal and immunodeficient mice. AU - Capilla,Javier, AU - Maffei,Claudia M L, AU - Clemons,Karl V, AU - Sobel,Raymond A, AU - Stevens,David A, PY - 2006/10/31/pubmed PY - 2007/1/17/medline PY - 2006/10/31/entrez SP - 601 EP - 10 JF - Medical mycology JO - Med Mycol VL - 44 IS - 7 N2 - Cryptococcus neoformans (Cn) var. grubii or Cryptococcus neoformans var. neoformans infection is usually associated with immunocompromised hosts, whereas Cryptococcusgattii more frequently causes disease in immunocompetent hosts. We examined the effects of immunodeficiency and glucocorticoid-induced immunosuppression on systemic murine infection induced by i.v. inoculation with these pathogens. SCID and immunocompetent BALB/c and C57BL/6 mice were infected with <or=107 yeast of Cn var. grubii or C. gattii; immunosuppressed BALB/c mice were infected with <or=106 yeast. Mortality was inoculum size-dependent in each model system, for both organisms. Following infection with 106 CFU of either Cn var. grubii or C. gattii immunocompetent BALB/c mice survived longer than immunosuppressed mice (P<0.0001 in both cases); no differences were found using lower inocula. SCID mice infected with Cn var. grubii or C. gattii died sooner than BALB/c mice (P<0.0013, all comparisons). Unexpectedly, BALB/c mice infected with C. gattii developed external lesions. Immunocompetent mice developed rectal prolapse more frequently whereas immunosuppressed mice developed more frequent skin lesions, predominantly on the tail. The fungal burden was especially high in rectum, skin and lung tissues. Histologic examination showed extensive infection of the rectum and skin and pneumonitis. Determination of CFU from various organs of immunocompetent BALB/c mice infected i.v. with 105 CFU of C. gattii or Cn var. grubii showed significant temporal increase of burdens of Cn var. grubii in brain and liver (P<0.003); other organs showed decreasing fungal burden. C.gattii was recovered only from liver and lungs, no CFU were detected in the other organs. As opposed to epidemiologic observations, our results demonstrate no predilection by C. gattii for infection of immunocompetent over immunosuppressed hosts; immunosuppression increased the risk of severe cryptococcosis by both varieties, especially at high inocula. This is the first report of C. gattii inducing experimental cutaneous and intestinal mucosal infection; Cn var. grubii did not affect these tissues, indicating differences in tissue tropism of these pathogens. SN - 1369-3786 UR - https://www.unboundmedicine.com/medline/citation/17071553/Experimental_systemic_infection_with_Cryptococcus_neoformans_var__grubii_and_Cryptococcus_gattii_in_normal_and_immunodeficient_mice_ L2 - https://academic.oup.com/mmy/article-lookup/doi/10.1080/13693780600810040 DB - PRIME DP - Unbound Medicine ER -