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High body temperature increases gut microbiota-dependent host resistance to influenza A virus and SARS-CoV-2 infection

Authors :
Minami Nagai
Miyu Moriyama
Chiharu Ishii
Hirotake Mori
Hikaru Watanabe
Taku Nakahara
Takuji Yamada
Dai Ishikawa
Takamasa Ishikawa
Akiyoshi Hirayama
Ikuo Kimura
Akihito Nagahara
Toshio Naito
Shinji Fukuda
Takeshi Ichinohe
Source :
Nature Communications, Vol 14, Iss 1, Pp 1-13 (2023)
Publication Year :
2023
Publisher :
Nature Portfolio, 2023.

Abstract

Abstract Fever is a common symptom of influenza and coronavirus disease 2019 (COVID-19), yet its physiological role in host resistance to viral infection remains less clear. Here, we demonstrate that exposure of mice to the high ambient temperature of 36 °C increases host resistance to viral pathogens including influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High heat-exposed mice increase basal body temperature over 38 °C to enable more bile acids production in a gut microbiota-dependent manner. The gut microbiota-derived deoxycholic acid (DCA) and its plasma membrane-bound receptor Takeda G-protein-coupled receptor 5 (TGR5) signaling increase host resistance to influenza virus infection by suppressing virus replication and neutrophil-dependent tissue damage. Furthermore, the DCA and its nuclear farnesoid X receptor (FXR) agonist protect Syrian hamsters from lethal SARS-CoV-2 infection. Moreover, we demonstrate that certain bile acids are reduced in the plasma of COVID-19 patients who develop moderate I/II disease compared with the minor severity of illness group. These findings implicate a mechanism by which virus-induced high fever increases host resistance to influenza virus and SARS-CoV-2 in a gut microbiota-dependent manner.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
14
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.751754dc12254778afd6f740e9152c9e
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-023-39569-0