Differences in Host Innate Responses among Coccidioides Isolates in a Murine Model of Pulmonary Coccidioidomycosis
Eric R G Lewis1, Victoria R David2, Adina L Doyle3
1Northern Arizona Center for Valley Fever Research, Division of Pathogen Genomics, Translational Genomics Research Institute North, Flagstaff, Arizona, USA Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA Valley Fever Center for Excellence, University of Arizona, Tucson, Arizona, USA.
Abstract:
Coccidioides immitis and Coccidioides posadasii are soil-dwelling fungi and the causative agents of coccidioidomycosis, a mycosis endemic to certain semiarid regions in the Americas. The most common route of infection is by inhalation of airborne Coccidioides arthroconidia. Once a susceptible host inhales the conidia, a transition to mature endosporulated spherules can occur within the first 5 days of infection. For this study, we examined the host response in a murine model of coccidioidomycosis during a time period of infection that has not been well characterized. We collected lung tissue and bronchoalveolar lavage fluid (BALF) from BALB/c mice that were infected with a C. immitis pure strain, a C. immitis hybrid strain, or a C. posadasii strain as well as uninfected mice. We compared the host responses to the Coccidioides strains used in this study by assessing the level of transcription of selected cytokine genes in lung tissues and characterized host and fungal proteins present in BALF. Host response varied depending on the Coccidioides strain that was used and did not appear to be overly robust. This study provides a foundation to begin to dissect the host immune response early in infection, to detect abundant Coccidioides proteins, and to develop diagnostics that target these early time points of infection.
