Pulmonary phagocyte-derived NPY and Y1 receptor axis controls the pathology of severe influenza virus infection

[Speaker] Yumiko Imai:1
[Co-author] Midori Hoshizaki:1, Yu Ichida:1, Herbert Herzog:2, Josef Penninger:3, Keiji Kuba:4
1:National Institute of Biomedical Innovation, Health and Nutrition, Japan, 2:Garvan Institute of Medical Research, Sydney, Australia, 3:Biotechnology in the Austrian Academy of Sciences, Vienna, Austria, 4:Akita University Faculty of Medicine, Akita, Japan

Cross-talk between the autonomic nervous system and the immune system is considered an important biological process. In addition to the sympathetic nerve-derived neural catecholamines (CA), phagocytes-derived CA can regulate pulmonary inflammation. Besides CA, sympathetic nerves also release neuropeptide Y (NPY) upon stimulation. However, it remains unknown if any non-neural sources of NPY may play a role in severe influenza virus infection. Here we show that de novo synthesis of NPY was increased in phagocytes in lungs following influenza virus infection. Genetic deletion of Npy or Y1r specifically in phagocytes greatly improved the pathology of severe influenza virus infection. Mechanistically, NPY signalling through Y1R on phagocytes is critical for the induction of suppressor of cytokine signaling 3 (SOCS3), consequently impairing anti-viral response and promoting pro-inflammatory cytokine production Thus, regulation of NPY-Y1R-SOCS3 pathways on phagocytes could act as a fine-tuner of an innate immune response, which could be a therapeutic target for severe influenza virus infection.
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