Giardia Infection of the Small Intestine Induces Chronic Colitis in Genetically Susceptible Hosts.
Giardia Infection of the Small Intestine Induces Chronic Colitis in Genetically Susceptible Hosts.
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DOI：
10.4049/jimmunol.1700824
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发表时间：
2018-07-15
期刊：
影响因子：
--
通讯作者：
Eckmann L
中科院分区：
文献类型：
--
作者：
Dann SM;Le CHY;Hanson EM;Ross MC;Eckmann L
贾第鞭毛虫是一种寄生在管腔内的原生动物，它是世界范围内引起肠道疾病的重要寄生虫。感染可以持续很长一段时间，肠道炎症最小，这表明贾第虫可能会减弱宿主的反应，以确保其生存，但在大多数情况下，最终发生清除。IL-10是一种抗炎调节剂，对肠道内稳态和控制宿主对细菌暴露的反应至关重要，但其在协调肠道中抗原动物宿主防御中的潜在作用尚不清楚。在这里，我们发现，小鼠感染天然肠道病原体，贾第鞭毛虫，诱导短暂的IL-10反应后2-4周，在原发部位的感染在小肠上部，但寄生虫定植和根除不受影响的细胞因子在基因靶向小鼠的情况下。然而，IL-10对于控制结肠中感染相关的免疫学后遗症至关重要，因为在感染后1-2周内在IL-10缺陷小鼠中观察到严重和持续的腹泻和结肠炎，而在未感染的同窝对照中未观察到。炎症的特征是上皮增生，中性粒细胞和巨噬细胞的扩张，和Th 1诱导，并可以通过阻断IL-12/IL-23 p40，但不能耗尽的CD 11 c树突状细胞。此外，肠道微生物群的组成发生了特征性变化，并且是疾病所必需的，因为抗生素和MyD 88缺陷小鼠TLR信号的丧失可以保护其免受结肠炎的侵害。总之，我们的数据表明，由管腔和看似非炎性病原体引起的短暂感染可在遗传易感宿主中引发持续性结肠炎，这对理解感染后综合征和其他慢性肠道炎症具有更广泛的意义。
The lumen-dwelling protozoan, Giardia, is an important parasitic cause of diarrheal disease worldwide. Infection can persist over extended periods with minimal intestinal inflammation, suggesting that Giardia may attenuate host responses to ensure its survival, although clearance eventually occurs in most cases. IL-10 is an anti-inflammatory regulator critical for intestinal homeostasis and controlling host responses to bacterial exposure, yet its potential role in coordinating antiprotozoal host defense in the intestine is not known. Here, we found that murine infection with the natural enteric pathogen, Giardia muris, induced a transient IL-10 response after 2–4 weeks at the primary site of infection in the upper small intestine, but parasite colonization and eradication were not affected by the absence of the cytokine in gene-targeted mice. However, IL-10 was critical for controlling infection-associated immunological sequelae in the colon, because severe and persistent diarrhea and colitis were observed in IL-10 deficient mice within 1–2 weeks after infection but not in uninfected littermate controls. Inflammation was characterized by epithelial hyperplasia, neutrophil and macrophage expansion, and Th1 induction, and could be prevented by blockade of IL-12/IL-23 p40 but not depletion of CD11c dendritic cells. Furthermore, the intestinal microbiota underwent characteristic shifts in composition and was required for disease, since antibiotics and loss of TLR signaling in MyD88-deficient mice protected against colitis. Together, our data suggest that transient infection by a luminal and seemingly non-inflammatory pathogen can trigger sustained colitis in genetically susceptible hosts, which has broader implications for understanding post-infectious syndromes and other chronic intestinal inflammatory conditions.
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影响因子：
5.3
作者：
Halliez MC;Buret AG
通讯作者：
Buret AG
DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
32.4
作者：
Hou, Baidong;Reizis, Boris;DeFranco, Anthony L.
通讯作者：
DeFranco, Anthony L.
影响因子：
3.1
作者：
Dann, Sara M.;Le, Christine;Eckmann, Lars
通讯作者：
Eckmann, Lars
影响因子：
4
作者：
Beatty, Jennifer K.;Akierman, Sarah V.;Buret, Andre G.
通讯作者：
Buret, Andre G.