Commensal Cryptosporidium colonization elicits a cDC1-dependent Th1 response that promotes intestinal homeostasis and limits other infections.
Commensal Cryptosporidium colonization elicits a cDC1-dependent Th1 response that promotes intestinal homeostasis and limits other infections.
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共生隐孢子虫定植激发cDC1依赖性Th1反应，促进肠道内稳态和限制其他感染。
DOI：
10.1016/j.immuni.2021.10.002
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发表时间：
2021-11-09
期刊：
影响因子：
32.4
通讯作者：
Hsieh CS
中科院分区：
文献类型：
--
作者：
Russler-Germain EV;Jung J;Miller AT;Young S;Yi J;Wehmeier A;Fox LE;Monte KJ;Chai JN;Kulkarni DH;Funkhouser-Jones LJ;Wilke G;Durai V;Zinselmeyer BH;Czepielewski RS;Greco S;Murphy KM;Newberry RD;Sibley LD;Hsieh CS
隐孢子虫可引起严重腹泻和发病，但许多感染是无症状的。在这里，我们研究了免疫反应的隐孢子虫tyzzeri（Ct-STL）偶然发现时，传统的1型树突状细胞（cDC 1）缺陷型小鼠隐孢子虫病。Ct-STL在野生型小鼠中垂直传播，没有负面健康影响。然而，Ct-STL引起肠道免疫系统的深刻变化，包括诱导产生IFNγ的Th 1应答。T细胞受体测序结合常见Th 1 TCR的体外和体内分析显示，Ct-STL引起显性抗原特异性Th 1应答。相比之下，cDC 1 s缺陷使Ct-STL CD 4 T细胞应答偏向Th 17和调节性T细胞。虽然Ct-STL主要定植于小肠，但结肠Th 1应答增强，并与预防啮齿类柠檬酸杆菌感染和葡聚糖硫酸钠加重以及抗IL 10 R触发的结肠炎相关。因此，Ct-STL代表了一种肠道致病菌，它能增强Th 1介导的肠道稳态，这可能反映了无症状的人类隐孢子虫感染。隐孢子虫是一种原生动物寄生虫，在世界范围内引起人类和动物的胃肠道疾病。我们确定了一个隐孢子虫tyzzeri流行在我们的老鼠殖民地。这种隐孢子虫菌株不会引起野生型小鼠的疾病，但会改变肠道免疫系统的组成和功能。
Cryptosporidium can cause severe diarrhea and morbidity, but many infections are asymptomatic. Here, we studied the immune response to a commensal strain of Cryptosporidium tyzzeri (Ct-STL) serendipitously discovered when conventional type 1 dendritic cell (cDC1)-deficient mice developed cryptosporidiosis. Ct-STL was vertically transmitted without negative health effects in wild-type mice. Yet, Ct-STL provoked profound changes in the intestinal immune system, including induction of an IFNγ-producing Th1 response. T cell receptor sequencing coupled with in vitro and in vivo analysis of common Th1 TCRs revealed that Ct-STL elicited a dominant antigen-specific Th1 response. By contrast, deficiency in cDC1s skewed the Ct-STL CD4 T cell response toward Th17 and regulatory T cells. Although Ct-STL predominantly colonized the small intestine, colon Th1 responses were enhanced and associated with protection against Citrobacter rodentium infection and exacerbation of dextran sodium sulfate and anti-IL10R-triggered colitis. Thus, Ct-STL represents a commensal pathobiont that elicits Th1-mediated intestinal homeostasis that may reflect asymptomatic human Cryptosporidium infection. Cryptosporidium are protozoan parasites that cause gastrointestinal illness in humans and animals worldwide. We identified a commensal strain of Cryptosporidium tyzzeri endemic in our mouse colony. This strain of Cryptosporidium does not cause disease in wild-type mice but changes the composition and function of the intestinal immune system.
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DOI：
10.1084/jem.20161776
发表时间：
2016-12-12
期刊：
The Journal of experimental medicine
影响因子：
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作者：
Escalante NK;Lemire P;Cruz Tleugabulova M;Prescott D;Mortha A;Streutker CJ;Girardin SE;Philpott DJ;Mallevaey T
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64.5
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Chudnovskiy, Aleksey;Mortha, Arthur;Kana, Veronika;Kennard, Andrea;Ramirez, Juan David;Rahman, Adeeb;Remark, Romain;Mogno, Ilaria;Ng, Ruby;Gnjatic, Sasha;Amir, El-ad David;Solovyov, Alexander;Greenbaum, Benjamin;Clemente, Jose;Faith, Jeremiah;Belkaid, Yasmine;Grigg, Michael E.;Merad, Miriam
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DOI：
10.1073/pnas.1000080107
发表时间：
2011-03-15
影响因子：
11.1
作者：
Caporaso, J. Gregory;Lauber, Christian L.;Knight, Rob
通讯作者：
Knight, Rob