The goal of the BL3 Animal Core is to provide a murine model of coccidioidomycosis to study the host- pathogen interactions in the respiratory tract in order to understand the early immunologic events that lead to either resolution of infection or progression with development of clinical disease. Both host and pathogen factors will be studied. Variably susceptible inbred strains of mice (BALB/c, C57BL/6, and DBA/2N) will be challenged intranasally with lethal and non-lethal strains of Coccidioides spp. and lung tissue collected sequentially. Assays will be performed to evaluate differential 1) gene expression in the fungus, and 2) leukocyte and cytokine profiles in the different mouse strains. Lung lesions will be compared histologically in mice resolving vs. failing to control infection. The objectives of the Core are 1) to infect and monitor mice for the studies, 2) collect and preserve lung tissue for Projects 1 and 2, 3) perform bronchoalveolar lavage on specified animals and preserve the specimens, 4) provide subjective evaluation of clinical/post-ortem condition of animals during experiments. The BL3 Animal Core provides a means for the Projects to obtain lung tissue from mice intranasally infected with Coccidioides, a Biosafety Level 3 air-borne pathogen and a CDC/USDA Select Agent with a significant risk of respiratory exposure to workers unless handled under proper containment conditions. The intranasal model in the mouse allows researchers to study early events in an infection similar to natural inhalation exposure of humans. Understanding early events will help ascertain what aspects of the immune response can be manipulated to prevent disease, reverse a poor immune response, or signal the pathogen to go into an arrested state that is walled off by the host, leading to containment of disease. Even in a population of normal humans, a preventive approach will reduce morbidity associated with coccidioidal infection.
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