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- Title
A Chronic Murine Disease Model of Coccidioidomycosis Using Coccidioides posadasii, Strain 1038.
- Authors
Shubitz, Lisa F; Powell, Daniel A; Butkiewicz, Christine D; Lewis, M Lourdes; Trinh, Hien T; Frelinger, Jeffrey A; Orbach, Marc J; Galgiani, John N
- Abstract
Murine infections with most Coccidioides spp. strains are lethal by 3 weeks, limiting the study of immune responses. Coccidioides posadasii, strain 1038 (Cp1038), while slowly lethal, resulted in protracted survival of C57BL/6 (B6) mice. In resistant (B6D2)F1/J mice, lung fungal burdens stabilized by week 4 without progression through week 16, better modeling human coccidioidal infections after their immunologic control. Immunodeficient tumor necrosis factor (Tnf) α knockout (KO) and interferon (Ifn) γ receptor 1 (Ifn-γr1) KO mice survived a median of 22.5 and 34 days, compared with 70 days in B6 mice (P = .001 and P < .01, respectively), though 14-day lung fungal burden studies showed little difference between Ifn-γr1 KO and B6 mice. B6 mice showed peak concentrations of key inflammatory lung cytokines, including interleukin 6, 23, and 17A, Tnf-α, and Ifn-γ, only after 4 weeks of infection. The slower progression in B6 and the acquired fungal burden stability in B6D2 mice after Cp1038 infection greatly increases the array of possible immunologic studies.
- Subjects
TUMOR necrosis factors; MEDICAL model; CHRONIC diseases; COCCIDIOIDOMYCOSIS; LUNG microbiology; BIOLOGICAL models; ANIMAL experimentation; FUNGI; RESEARCH funding; MICE
- Publication
Journal of Infectious Diseases, 2021, Vol 223, Issue 1, p166
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiaa419