In the context of our interest in host-pathogen interactions, we are pursuing currently the following projects:
We have developed a novel mouse model to study the mechanisms of commensalism, from the standpoint of both the host and bacterium. The model involves noninvasive inoculation of the well-studied lab mouse with a new commensal Neisseria species isolated from the normal flora of healthy wild mice. The model allows studies of colonization, and the elusive process of persistence, in a variety of mucosal niches, from the relatively well-studied intestinal tract to the less well-studied respiratory tract and oral cavity. Experimentation is guided by a vast store of knowledge on the mouse and close relatives of the bacterium. Using this unique model, we will identify immune processes and mouse genes critical for susceptibility to N. tucsonensis colonization and bacterial genes critical for colonization and persistence.
Coccidioidomycosis is a serious respiratory disease in the Sonoran Desert of southern Arizona and the central valley of California. There is currently no effective vaccine; some people can require life-long treatment with expensive antifungals. The goal of this project is to understand the mechanism of protective immunity elicited by a novel attenuated mutant of Coccidioides, Δcps1. Preliminary data demonstrates both safety (no disease in profoundly immunocompromised mice) and profound protection from subsequent infection with wild-type Coccidioides in otherwise susceptible mice. Information is incomplete concerning the immune response(s) induced vaccination and which are responsible for protection are unknown. Here we will use the approaches of modern cellular immunology to determine the cellular mechanism of vaccination and which of the induced responses to Δcps1 are responsible for protection.