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

IF 20.6 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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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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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.