Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity

Nat Immunol. 2011 May 29;12(7):631-8. doi: 10.1038/ni.2045.


Patients with asthma, a major public health problem, are at high risk for serious disease from influenza virus infection, but the pathogenic mechanisms by which influenza A causes airway disease and asthma are not fully known. We show here in a mouse model that influenza infection acutely induced airway hyper-reactivity (AHR), a cardinal feature of asthma, independently of T helper type 2 (T(H)2) cells and adaptive immunity. Instead, influenza infection induced AHR through a previously unknown pathway that required the interleukin 13 (IL-13)-IL-33 axis and cells of the non-T cell, non-B cell innate lymphoid type called 'natural helper cells'. Infection with influenza A virus, which activates the NLRP3 inflammasome, resulted in much more production of IL-33 by alveolar macrophages, which in turn activated natural helper cells producing substantial IL-13.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Asthma / immunology
  • Asthma / physiopathology
  • Bronchial Hyperreactivity / immunology*
  • Carrier Proteins / immunology
  • Female
  • Immunity, Innate
  • Influenza A virus / immunology
  • Interleukin-13 / immunology
  • Interleukin-33
  • Interleukins / immunology
  • Lymphocytes / immunology*
  • Macrophages, Alveolar / immunology
  • Mice
  • Mice, Inbred BALB C
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Orthomyxoviridae Infections / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology


  • Carrier Proteins
  • Il33 protein, mouse
  • Interleukin-13
  • Interleukin-33
  • Interleukins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse