HOST FACTORS MEDIATE INVASION BY CAMPYLOBACTER JEJUNI

描述(摘自申请者的摘要)：空肠弯曲杆菌 是美国和美国人类肠道感染的主要原因 已被美国疾病控制与预防中心列为新发疾病。这 细菌机会性地侵入胃肠道，尤其是 结肠，引起胃肠炎、直肠炎，偶尔还会引起其他 问题，但控制这次入侵的因素在很大程度上是未知的。 长期目标：了解抗药性的机制 空肠弯曲菌对胃肠道的机会性入侵； 为检测细胞因子和疫苗疗法提供了新的动物模型。 人类的空肠病。这项建议是基于调查人员的 之前对猪模型的研究表明，在肠道感染之后 在猪旋毛虫的感染下，空肠弯曲杆菌侵入猪的结肠。机制： 空肠弯曲菌对黏膜侵袭的抵抗力尚不清楚。 其目的是确定猪分支杆菌促进 空肠弯曲菌对仔猪结肠宿主细胞的入侵。假设是 测试表明，猪圆线虫允许空肠弯曲菌通过直接作用于 带有促进空肠弯曲菌摄取的分泌性介质的细胞，或2) 通过刻板的免疫或促炎反应间接起作用 下调宿主细胞对空肠弯曲菌入侵的抵抗力。 具体目的：1)确定空肠弯曲菌侵袭T。 猪空肠弯曲菌感染猪，2)确定血清型 细胞因子模式与空肠弯曲菌侵袭宿主细胞有关，3) 确定空肠弯曲菌的侵袭是否由于直接作用而促进 蠕虫的某些分泌/排泄产物，以及4)确定哪种宿主 在空肠弯曲菌入侵过程中，细胞基因的表达存在差异。

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.