Circadian control of lung inflammation in influenza infection

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.

Melatonin: Roles in influenza, Covid‐19, and other viral infections

“…Preclinical data show that irrespective of the viral burden, survival following influenza viral infection is determined by the circadian influence on the patterning of the immune response. 25 The circadian gene, Bmal1, is a significant inhibitor of herpes simplex virus (HSV)-1 and influenza viruses, highlighting the role of circadian factors in the regulation of viral infections. 26 As the loss of the circadian rhythm can increase viral replication, viruses can act to sabotage circadian regulation, exemplified by HSV-1 suppression of Bmal1.…”

Glucocorticoids Regulate Circadian Rhythm of Innate and Adaptive Immunity

“…Immune response against L. monocytogenes was induced strongly at ZT8 compared to ZT0, and BMAL1 regulated the circadian changes of the distribution, cytokine production, and bacterial rejection by monocytes. Sengupta et al, showed that BMAL1 regulated the diurnal difference of inflammation against influenza A virus which is induced strongly at the active phase via the monocyte infiltration in lung (62). Next, Fortier et al, found that T cell proliferation after anti-CD3 antibody stimulation became higher at the late rest or the active phase (circadian time (CT) 10-14) in a circadian manner, probably because of oscillating ZAP-70 expression with peak at CT 8 (63).…”

The mediating role of sleep, physical activity, and diet in the association between shift work and respiratory infections

“…Coefficients are adjusted for age, gender, occupation, influenza vaccination status, and general perceived health. a P<0.05. be at increased risk for respiratory infections (29). Two epidemiological studies that examined the relation between shift work and infectious diseases also found an increased incidence of infectious diseases among shift workers (30,31), but one study reported that infectious diseases were more common among non-shift workers (32).…”