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

Circadian control of lung inflammation in influenza infection.

Author information

1
Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. SenguptaS@email.chop.edu.
2
Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, 19104, USA. SenguptaS@email.chop.edu.
3
Institute of Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
4
Systems Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
5
Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
6
Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
7
University of Pennsylvania Veterinary School, Philadelphia, PA, 19104, USA.

Abstract

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.

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