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

ABSTRACT: While a common symptom of influenza and coronavirus disease 2019 (COVID-19) is fever, its physiological role on host resistance to viral infection remains less clear. Here, we demonstrate that exposure of mice to the high ambient temperature of 36 °C increase 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 hamster from lethal SARS-CoV-2 infection. Moreover, we demonstrate that certain bile acids are reduced in the plasma of COVID-19 patients who developed moderate I/II disease compared with minor illness group. These findings uncover an unexpected mechanism by which virus-induced high fever increases host resistance to influenza virus and SARS-CoV-2 in a gut microbiota-dependent manner.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Intestine

DISEASE(S): Covid-19,Influenza

SUBMITTER: Shinji Fukuda

PROVIDER: ST002476 | MetabolomicsWorkbench | Tue Jan 24 00:00:00 GMT 2023

REPOSITORIES: MetabolomicsWorkbench

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

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