HOST FACTORS MEDIATE INVASION BY CAMPYLOBACTER JEJUNI

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DESCRIPTION (Adapted from the applicant's abstract): Campylobacter jejuni is the leading cause of intestinal infection in humans in the US and the world, and has been designated as an emerging disease by the US CDC. This bacterium opportunistically invades the gastrointestinal tract, especially the colon, causing gastroenteritis, proctitis, and occasionally other problems, but the factors controlling this invasion are largely unknown. Long-range goal: to understand the mechanisms of resistance to opportunistic invasion of the gastrointestinal tract by C. jejuni; to provide a new animal model for testing cytokine and vaccine therapies for C. jejuni disease in humans. The proposal is based on the investigators previous work with a swine model wherein subsequent to intestinal infection with Trichuris suis, C. jejuni invades the swine colon. Mechanisms of resistance to mucosal invasion by C. jejuni are unknown. The objective is to determine the mechanism whereby T. suis facilitates the invasion of host cells by C. jejuni in piglet colons. The hypothesis to be tested is that T. suis allows C. jejuni to invade 1) by acting directly on cells with a secreted mediator to facilitate uptake of C. jejuni, or 2) acting indirectly through stereotypic immune or proinflammatory responses to downregulate resistance of host cells to C. jejuni invasion. Specific Aims: 1) Determine what cell types are invaded by C. jejuni in T. suis induced C. jejuni infections in swine, 2) Determine whether serotype cytokine patterns are associated with C. jejuni invasion of host cells, 3) Determine whether C. jejuni invasion is facilitated due to a direct effect of some secreted/excreted product of the worms, and 4) Determine what host cell genes are differentially expressed during C. jejuni invasion.