Intestinal epithelial tuft cell induction is negated by a murine helminth and its secreted products.
Intestinal epithelial tuft cell induction is negated by a murine helminth and its secreted products.
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DOI：
10.1084/jem.20211140
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发表时间：
2022-01-03
期刊：
影响因子：
--
通讯作者：
Maizels RM
中科院分区：
文献类型：
--
作者：
Drurey C;Lindholm HT;Coakley G;Poveda MC;Löser S;Doolan R;Gerbe F;Jay P;Harris N;Oudhoff MJ;Maizels RM
肠蠕虫Heligmosomoides polygyrus通过在肠类器官中和在体内施用时阻断簇细胞的分泌因子抑制上皮簇细胞的发育，所述上皮簇细胞对于2型免疫应答是必需的。蠕虫寄生虫是免疫系统的熟练操纵者，使用多种策略来逃避宿主2型反应。在肠道生态位中，上皮细胞对于通过簇状细胞启动2型免疫至关重要，簇状细胞与杯状细胞一起响应于2型细胞因子IL-4和IL-13而急剧扩增。然而，目前尚不清楚蠕虫是否调节这些上皮细胞群。在体外，使用小肠类器官，我们发现来自Heligmosomoides polygyrus的排泄/分泌产物（HpES）阻断IL-4/13的作用，抑制簇状细胞和杯状细胞基因表达和扩增，并诱导胎儿上皮细胞的球状体生长特征和稳态修复。在暴露于寄生虫幼虫的类器官中观察到类似的结果。在体内，H. polygyrus感染抑制簇细胞对异源巴西日本圆线虫感染或琥珀酸的反应，并且HpES也减少琥珀酸刺激的簇细胞扩增。我们的研究结果表明，蠕虫寄生虫重塑他们的肠道环境，在一个新的战略，破坏主机的保护性反应。
The intestinal helminth Heligmosomoides polygyrus suppresses development of epithelial tuft cells, which are essential for the type 2 immune response, through secreted factors that block tuft cells both in intestinal organoids and when administered in vivo. Helminth parasites are adept manipulators of the immune system, using multiple strategies to evade the host type 2 response. In the intestinal niche, the epithelium is crucial for initiating type 2 immunity via tuft cells, which together with goblet cells expand dramatically in response to the type 2 cytokines IL-4 and IL-13. However, it is not known whether helminths modulate these epithelial cell populations. In vitro, using small intestinal organoids, we found that excretory/secretory products (HpES) from Heligmosomoides polygyrus blocked the effects of IL-4/13, inhibiting tuft and goblet cell gene expression and expansion, and inducing spheroid growth characteristic of fetal epithelium and homeostatic repair. Similar outcomes were seen in organoids exposed to parasite larvae. In vivo, H. polygyrus infection inhibited tuft cell responses to heterologous Nippostrongylus brasiliensis infection or succinate, and HpES also reduced succinate-stimulated tuft cell expansion. Our results demonstrate that helminth parasites reshape their intestinal environment in a novel strategy for undermining the host protective response.
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影响因子：
64.8
作者：
Gerbe F;Sidot E;Smyth DJ;Ohmoto M;Matsumoto I;Dardalhon V;Cesses P;Garnier L;Pouzolles M;Brulin B;Bruschi M;Harcus Y;Zimmermann VS;Taylor N;Maizels RM;Jay P
通讯作者：
Jay P
DOI：
10.1084/jem.20091268
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Herbert DR;Yang JQ;Hogan SP;Groschwitz K;Khodoun M;Munitz A;Orekov T;Perkins C;Wang Q;Brombacher F;Urban JF Jr;Rothenberg ME;Finkelman FD
通讯作者：
Finkelman FD
影响因子：
11.4
作者：
Jenny, M;Uhl, C;Gradwohl, G
通讯作者：
Gradwohl, G
影响因子：
1.2
作者：
Bialkowska, Agnieszka B.;Ghaleb, Amr M.;Yang, Vincent W.
通讯作者：
Yang, Vincent W.
影响因子：
9.6
作者：
Inclan-Rico JM;Siracusa MC
通讯作者：
Siracusa MC