Innate immune sensing of rotavirus by intestinal epithelial cells leads to diarrhea

IF 18.7 1区医学 Q1 MICROBIOLOGY

Cell host & microbe Pub Date : 2025-03-03 DOI:10.1016/j.chom.2025.02.005

Gaopeng Hou, Juhee Son, Maria Florencia Gomez Castro, Takahiro Kawagishi, Xingxing Ren, Alexa N. Roth, Avan Antia, Qiru Zeng, Anna L. DeVeaux, Ningguo Feng, Hinissan P. Kohio, Megan T. Baldridge, Terence S. Dermody, Shu Zhu, Siyuan Ding

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引用次数: 0

Abstract

Diarrhea is the predominant symptom of acute gastroenteritis resulting from enteric infections and a leading cause of death in infants and young children. However, the role of the host response in diarrhea pathogenesis is unclear. Using rotavirus and neonatal mice as a model, we found that oral inoculation of UV-inactivated replication-defective rotavirus consistently induced watery diarrhea by robust activation of cytosolic double-stranded RNA sensing pathways and type III interferon (IFN-λ) secretion. Diarrhea was significantly diminished in mice lacking the IFN-λ receptor. Mechanistically, IFN-λ signaling downregulates the expression of Dra, a chloride and bicarbonate exchanger, which contributes to reduced water absorption. We confirmed these findings in mice inoculated with reovirus, as well as in donor-derived human intestinal organoids and human biopsy samples. Our data highlight a mechanism of rapid diarrhea induction by host innate immune sensing in the gastrointestinal tract and suggest that diarrhea induction is an active host defense strategy to eliminate the pathogen.

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肠道上皮细胞对轮状病毒的先天免疫感应导致腹泻

腹泻是由肠道感染引起的急性胃肠炎的主要症状，也是婴幼儿死亡的主要原因。然而，宿主反应在腹泻发病机制中的作用尚不清楚。以轮状病毒和新生小鼠为模型，我们发现口服灭活的复制缺陷轮状病毒通过激活胞质双链RNA感应途径和III型干扰素（IFN-λ）分泌，持续诱导水样腹泻。缺乏IFN-λ受体的小鼠腹泻明显减少。从机制上讲，IFN-λ信号可以下调氯离子和碳酸氢盐交换剂Dra的表达，从而减少水分吸收。我们在接种呼肠孤病毒的小鼠以及供体来源的人类肠道类器官和人类活检样本中证实了这些发现。我们的数据强调了宿主胃肠道先天免疫感应快速诱导腹泻的机制，并表明腹泻诱导是一种主动的宿主防御策略，以消除病原体。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell host & microbe 生物-微生物学

CiteScore

45.10

自引率

1.70%

发文量

201

审稿时长

4-8 weeks

期刊介绍： Cell Host & Microbe is a scientific journal that was launched in March 2007. The journal aims to provide a platform for scientists to exchange ideas and concepts related to the study of microbes and their interaction with host organisms at a molecular, cellular, and immune level. It publishes novel findings on a wide range of microorganisms including bacteria, fungi, parasites, and viruses. The journal focuses on the interface between the microbe and its host, whether the host is a vertebrate, invertebrate, or plant, and whether the microbe is pathogenic, non-pathogenic, or commensal. The integrated study of microbes and their interactions with each other, their host, and the cellular environment they inhabit is a unifying theme of the journal. The published work in Cell Host & Microbe is expected to be of exceptional significance within its field and also of interest to researchers in other areas. In addition to primary research articles, the journal features expert analysis, commentary, and reviews on current topics of interest in the field.