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Pulmonary phagocyte-derived NPY controls the pathology of severe influenza virus infection


Crosstalk between the autonomic nervous system and the immune system by means of the sympathetic and parasympathetic pathways is a critical process in host defence. Activation of the sympathetic nervous system results in the release of catecholamines as well as neuropeptide Y (NPY). Here, we investigated whether phagocytes are capable of the de novo production of NPY, as has been described for catecholamines. We show that the synthesis of NPY and its Y1 receptor (Y1R) is increased in phagocytes in lungs following severe influenza virus infection. The genetic deletion of Npy or Y1r specifically in phagocytes greatly improves the pathology of severe influenza virus infection, which is characterized by excessive virus replication and pulmonary inflammation. Mechanistically, it is the induction of suppressor of cytokine signalling 3 (SOCS3) via NPY-Y1R activation that is responsible for impaired antiviral response and promoting pro-inflammatory cytokine production, thereby enhancing the pathology of influenza virus infection. Thus, direct regulation of the NPY-Y1R-SOCS3 pathway on phagocytes may act as a fine-tuner of an innate immune response to virus infection, which could be a therapeutic target for lethal influenza virus infection.

Type Journal
ISBN 2058-5276 (Electronic) 2058-5276 (Linking)
Authors Fujiwara, S.; Hoshizaki, M.; Ichida, Y.; Lex, D.; Kuroda, E.; Ishii, K. J.; Magi, S.; Okada, M.; Takao, H.; Gandou, M.; Imai, H.; Hara, R.; Herzog, H.; Yoshimura, A.; Okamura, H.; Penninger, J. M.; Slutsky, A. S.; Uhlig, S.; Kuba, K.; Imai, Y.
Responsible Garvan Author Prof Herbert Herzog
Publisher Name Nature Microbiology
Published Date 2019-02-04
Published Volume 4
Published Issue 2
Published Pages 258-268
Status Published in-print
DOI 10.1038/s41564-018-0289-1
URL link to publisher's version
OpenAccess link to author's accepted manuscript version