Circadian control of lung inflammation in influenza infection

Nature Communications

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[1] 0000 0004 1936 8972, grid.25879.31, Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, 19104, Philadelphia, PA, USA;0000 0004 1936 8972, grid.25879.31, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, 19104, Philadelphia, PA, USA;0000 0004 1936 8972, grid.25879.31, Institute of Translational Medicine and Therapeutics, University of Pennsylvania, 19104, Philadelphia, PA, USA;0000 0004 1936 8972, grid.25879.31, Institute of Translational Medicine and Therapeutics, University of Pennsylvania, 19104, Philadelphia, PA, USA;0000 0004 1936 8972, grid.25879.31, Institute of Translational Medicine and Therapeutics, University of Pennsylvania, 19104, Philadelphia, PA, USA;0000 0004 1936 8972, grid.25879.31, Department of Genetics, University of Pennsylvania Perelman School of Medicine, 19104, Philadelphia, PA, USA;0000 0004 1936 8972, grid.25879.31, Institute of Translational Medicine and Therapeutics, University of Pennsylvania, 19104, Philadelphia, PA, USA;0000 0004 1936 8972, grid.25879.31, Systems Pharmacology, University of Pennsylvania Perelman School of Medicine, 19104, Philadelphia, PA, USA;0000 0004 1936 8972, grid.25879.31, Institute of Translational Medicine and Therapeutics, University of Pennsylvania, 19104, Philadelphia, PA, USA;0000 0004 1936 8972, grid.25879.31, University of Pennsylvania Veterinary School, 19104, Philadelphia, PA, USA;0000 0004 1936 8972, grid.25879.31, University of Pennsylvania Veterinary School, 19104, Philadelphia, PA, USA;

DOI  :  10.1038/s41467-019-11400-9

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY