A Chronic Murine Disease Model of Coccidioidomycosis Using Coccidioides posadasii, Strain 1038

Lisa Shubitz, Daniel A. Powell, Christine D. Butkiewicz, M. Lourdes Lewis, Hien T. Trinh, Jeffrey A. Frelinger, Marc Joel Orbach, John N. Galgiani

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)166-173
Number of pages8
JournalThe Journal of infectious diseases
Volume223
Issue number1
DOIs
StatePublished - Jan 4 2021

Keywords

  • Coccidioides
  • B6D2
  • chronic
  • cytokines
  • interferon γ
  • mice
  • survival
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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