Tropism for tuft cells determines immune promotion of norovirus pathogenesis.

Tropism for tuft cells determines immune promotion of norovirus pathogenesis.
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DOI:
10.1126/science.aar3799
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发表时间:
2018-04-13
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Virgin HW
Virgin HW
中科院分区:
其他
文献类型:
--
作者:
Wilen CB;Lee S;Hsieh LL;Orchard RC;Desai C;Hykes BL Jr;McAllaster MR;Balce DR;Feehley T;Brestoff JR;Hickey CA;Yokoyama CC;Wang YT;MacDuff DA;Kreamalmayer D;Howitt MR;Neil JA;Cadwell K;Allen PM;Handley SA;van Lookeren Campagne M;Baldridge MT;Virgin HW

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宿主免疫和微生物组之间的复杂相互作用调节诺如病毒感染。然而,肠道病毒感染促进宿主免疫的机制仍不清楚。诺如病毒的细胞嗜性也是未知的。最近,我们确定了CD300lf作为鼠诺如病毒(MNoV)受体。在这里,我们表明,簇状细胞,一种罕见类型的肠上皮细胞,表达CD300lf,是小鼠肠道中的MNoV的靶细胞。我们发现,2型细胞因子,诱导簇细胞增殖,促进MnoV在体内感染。这些细胞因子可以取代肠道微生物群在促进病毒感染中的作用。这是第一次报道病毒感染簇细胞,并提供了深入了解免疫系统和微生物如何协调促进肠道病毒感染。
Complex interactions between host immunity and the microbiome regulate norovirus infection. However, the mechanism of host immune promotion of enteric virus infection remains obscure. The cellular tropism of noroviruses is also unknown. Recently, we identified CD300lf as a murine norovirus (MNoV) receptor. Here we show that tuft cells, a rare type of intestinal epithelial cell, express CD300lf and are the target cell for MNoV in the mouse intestine. We found that type 2 cytokines, which induce tuft cell proliferation, promote MNoV infection in vivo. These cytokines can replace the effect of commensal microbiota in promoting virus infection. This is the first report of viral infection of tuft cells and provides insight into how the immune system and microbes can coordinately promote enteric viral infection.
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