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微绒毛细胞嗜性决定诺如病毒发病机制中的免疫促进作用。

Tropism for tuft cells determines immune promotion of norovirus pathogenesis.

机构信息

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

Department of Microbiology and Immunology, University of Illinois at Chicago College of Medicine, Chicago, IL, USA.

出版信息

Science. 2018 Apr 13;360(6385):204-208. doi: 10.1126/science.aar3799.

DOI:10.1126/science.aar3799
PMID:29650672
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6039974/
Abstract

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. In this study, we have shown 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. Our work thus provides insight into how the immune system and microbes can coordinately promote enteric viral infection.

摘要

宿主免疫与微生物组之间的复杂相互作用调节诺如病毒感染。然而,宿主免疫促进肠道病毒感染的机制仍不清楚。诺如病毒的细胞嗜性也未知。最近,我们鉴定出 CD300lf 是一种鼠诺如病毒(MNoV)的受体。在这项研究中,我们表明,类簇细胞(一种罕见的肠道上皮细胞)表达 CD300lf,并且是小鼠肠道中 MNoV 的靶细胞。我们发现,诱导类簇细胞增殖的 2 型细胞因子可促进体内 MNoV 感染。这些细胞因子可以替代共生微生物群促进病毒感染的作用。因此,我们的工作提供了关于免疫系统和微生物如何协调促进肠道病毒感染的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2464/6039974/668e05bc99d2/nihms978350f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2464/6039974/832b7d9a42e0/nihms978350f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2464/6039974/35a030d7e922/nihms978350f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2464/6039974/a804755221ce/nihms978350f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2464/6039974/668e05bc99d2/nihms978350f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2464/6039974/832b7d9a42e0/nihms978350f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2464/6039974/35a030d7e922/nihms978350f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2464/6039974/a804755221ce/nihms978350f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2464/6039974/668e05bc99d2/nihms978350f4.jpg

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本文引用的文献

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Nat Microbiol. 2017 Dec;2(12):1586-1591. doi: 10.1038/s41564-017-0057-7. Epub 2017 Nov 6.
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Differentiation and Protective Capacity of Virus-Specific CD8 T Cells Suggest Murine Norovirus Persistence in an Immune-Privileged Enteric Niche.病毒特异性CD8 T细胞的分化与保护能力提示小鼠诺如病毒在免疫特权性肠道生态位中持续存在。
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Norovirus Cell Tropism Is Determined by Combinatorial Action of a Viral Non-structural Protein and Host Cytokine.
肠道黏膜免疫中簇状细胞-2型固有淋巴细胞回路的调控
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Membrane asymmetry facilitates murine norovirus entry and persistent enteric infection.膜不对称性促进小鼠诺如病毒进入并引发持续性肠道感染。
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Gut virome and its implications in the pathogenesis and therapeutics of inflammatory bowel disease.肠道病毒组及其在炎症性肠病发病机制和治疗中的意义。
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Enteric tuft cell inflammasome activation drives NKp46+ILC3 IL22 via PGD2 and inhibits Salmonella.肠道簇状细胞炎性小体激活通过前列腺素D2驱动NKp46⁺ILC3产生白细胞介素-22并抑制沙门氏菌。
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