HOST FACTORS MEDIATE INVASION BY CAMPYLOBACTER JEJUNI

性状（改编自申请人摘要）：空肠弯曲杆菌 是美国和美国人类肠道感染的主要原因。 世界，并已被美国CDC指定为一种新兴疾病。 这 细菌机会性地侵入胃肠道，特别是 结肠，引起胃肠炎，直肠炎，偶尔还有其他 问题，但控制这种入侵的因素在很大程度上是未知的。 长期目标：了解耐药机制 C.胃肠道的机会性侵袭。空肠 为检测细胞因子和疫苗治疗C. 人类空肠炎 该提案是基于调查人员 先前用猪模型进行的工作，其中在肠道感染后， 猪鞭虫（Trichuris suis）、C.空肠侵入猪结肠。 机制 对C.空肠未知。 目的是确定T. suis促进了 C.仔猪结肠空肠。 假设是 测试结果表明，T。suis允许C.空肠侵入1）通过直接作用于 细胞分泌介质，以促进C.空肠，或2） 通过刻板免疫或促炎反应间接作用于 下调宿主细胞对C.空肠侵犯。 具体目的：1）确定C.空肠T. suis诱导C.猪空肠感染，2）确定血清型 细胞因子模式与C.空肠侵入宿主细胞，3） 确定C.由于直接作用， 蠕虫的一些分泌/排泄产物，以及4）确定什么宿主 细胞基因在C.空肠侵犯。

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.