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

Seiki Fujiwara, Midori Hoshizaki, Yu Ichida, Dennis Lex, Etsushi Kuroda, Ken J. Ishii, Shigeyuki Magi, Mariko Okada, Hiroyuki Takao, Masahiro Gandou, Hirotaka Imai, Ryujiro Hara, Herbert Herzog, Akihiko Yoshimura, Hitoshi Okamura, Josef M. Penninger, Arthur S. Slutsky, Stefan Uhlig, Keiji Kuba, Yumiko Imai

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)258-268
Number of pages11
JournalNature Microbiology
Issue number2
Publication statusPublished - Feb 1 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology


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