High ambient temperature dampens adaptive immune responses to influenza A virus infection

• Published in: Proceedings of the National Academy of Sciences - PNAS 2019-02, Vol.116 (8), p.3118-3125
• Main Authors: Moriyama, Miyu, Ichinohe, Takeshi
• Format: Article
• Language: English
• Subjects: Adaptive control; Adaptive immunity; Adaptive Immunity - immunology; Ambient temperature; Animals; Autophagy; Biological Sciences; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell adhesion & migration; Cell migration; Climate change; Dendritic cells; Diet; Environmental effects; Exposure; Fatty acids; Fever; Food intake; Geographical distribution; Heat; Hot Temperature; Humans; Infections; Inflammasomes; Inflammasomes - immunology; Influenza; Influenza A; Influenza A virus - immunology; Influenza A virus - pathogenicity; Influenza, Human - immunology; Influenza, Human - prevention & control; Influenza, Human - virology; Lung - immunology; Lung - virology; Lungs; Lymph nodes; Lymphocytes; Lymphocytes T; Mice; Microbiota; Nutritional status; Phagocytosis; Phlebovirus - immunology; Phlebovirus - pathogenicity; PNAS Plus; Temperature effects; Thrombocytopenia; Vector-borne diseases; Viral infections; Viruses; Zika Virus - immunology; Zika Virus - pathogenicity; Zika Virus Infection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1815029116

Although climate change may expand the geographical distribution of several vector-borne diseases, the effects of environmental temperature in host defense to viral infection in vivo are unknown. Here, we demonstrate that exposure of mice to the high ambient temperature of 36 °C impaired adaptive immune responses against infection with viral pathogens, influenza, Zika, and severe fever with thrombocytopenia syndrome phlebovirus. Following influenza virus infection, the high heat-exposed mice failed to stimulate inflammasome-dependent cytokine secretion and respiratory dendritic cell migration to lymph nodes. Although commensal microbiota composition remained intact, the high heat-exposed mice decreased their food intake and increased autophagy in lung tissue. Induction of autophagy in room temperature-exposed mice severely impaired virus-specific CD8 T cells and antibody responses following respiratory influenza virus infection. In addition, we found that administration of glucose or dietary short-chain fatty acids restored influenza virus-specific adaptive immune responses in high heat-exposed mice. These findings uncover an unexpected mechanism by which ambient temperature and nutritional status control virus-specific adaptive immune responses.