Mycobacterium avium-phagocyte interactions in a murine infection model

Sam Houston State University, Huntsville TX

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Mycobacterium avium (M. avium) is an environmental organism causing opportunistic infections in man and animals of agricultural importance. M. avium is responsible for a broad range of human illnesses including disseminated disease in AIDS patients and localized pulmonary infection in patients with underlying chronic lung disease. Infection with M. avium poses recalcitrant public health problems due to the limited susceptibility of this organism to available antibiotics. Exposure to M. avium is quite common and in the vast majority of encounters, host defenses appear to be sufficient to control the organism. However, illness due to this organism causes considerable morbidity in AIDS patients and in patients with pulmonary disease or on immunosuppressive therapy. M. avium isolates vary greatly in virulence, for unclear reasons, and few virulence factors have been identified. Control of M. avium requires the activation and maintenance of a CD4+ T cell response, which occurs upon presentation of M. avium-derived peptides that are generated by phagocytosis and processing of the bacteria by professional antigen presenting cells (APC). A previous study of 41 strains of M. avium identified three pathogenic phenotypes (low virulent are cleared, medium virulent generate a persistent infection, and high virulent grow unrestricted) in a murine infection model. We hypothesize that the three classes of M. avium present with different in vivo growth rates as a result of their differential abilities to induce antigen-specific T cell responses, more specifically, the three classes differentially affect antigen processing and presentation by APCs. We propose to assess the interactions of three representative strains of M. avium with primary murine macrophages and dendritic cells to determine if and how antigen presentation is affected. The overall goal of this proposal is to discover potential M. avium virulence factors in hopes of defining novel therapeutic targets. [unreadable] [unreadable] Public health relevance: M. avium causes serious infections in AIDS patients and other predisposed groups. This research will lead to a better understanding of how the bacterium infects humans, and therefore lead to new treatments. [unreadable] [unreadable]