Circadian control of lung inflammation in influenza infection

Nat Commun. 2019 Sep 11;10(1):4107. doi: 10.1038/s41467-019-11400-9.


Influenza is a leading cause of respiratory mortality and morbidity. While inflammation is essential for fighting infection, a balance of anti-viral defense and host tolerance is necessary for recovery. Circadian rhythms have been shown to modulate inflammation. However, the importance of diurnal variability in the timing of influenza infection is not well understood. Here we demonstrate that endogenous rhythms affect survival in influenza infection. Circadian control of influenza infection is mediated by enhanced inflammation as proven by increased cellularity in bronchoalveolar lavage (BAL), pulmonary transcriptomic profile and histology and is not attributable to viral burden. Better survival is associated with a time dependent preponderance of NK and NKT cells and lower proportion of inflammatory monocytes in the lung. Further, using a series of genetic mouse mutants, we elucidate cellular mechanisms underlying circadian gating of influenza infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / deficiency
  • ARNTL Transcription Factors / metabolism
  • Animals
  • Antigens, Ly
  • Circadian Rhythm / physiology*
  • Female
  • Influenza A virus / physiology
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / metabolism
  • Myeloid Cells / metabolism
  • Natural Killer T-Cells / immunology
  • Orthomyxoviridae Infections / complications*
  • Orthomyxoviridae Infections / genetics
  • Orthomyxoviridae Infections / physiopathology*
  • Orthomyxoviridae Infections / virology
  • Phenotype
  • Pneumonia / complications*
  • Pneumonia / physiopathology*
  • Pneumonia / virology
  • Time Factors
  • Transcriptome / genetics
  • Virus Replication


  • ARNTL Transcription Factors
  • Antigens, Ly
  • Arntl protein, mouse
  • Ly-6C antigen, mouse