Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice

Le résumé fourni par la source

Circadian rhythms control the diurnal nature of many physiological, metabolic, and immune processes. We hypothesized that age-related impairments in circadian rhythms are associated with high susceptibility to bacterial respiratory tract infections. Our data show that the time-of-day difference in the control of Streptococcus pneumoniae infection is altered in elderly mice. A lung circadian transcriptome analysis revealed that aging alters the daily oscillations in the expression of a specific set of genes and that some pathways that are rhythmic in young-adult mice are non-rhythmic or time shifted in elderly mice. In particular, the circadian expression of the clock component Rev-erb-α and apelin/apelin receptor was altered in elderly mice. In young-adult mice, we discovered an interaction between Rev-erb-α and the apelinergic axis that controls host defenses against S. pneumoniae via alveolar macrophages. Pharmacological repression of Rev-erb-α in elderly mice resulted in greater resistance to pneumococcal infection. These data suggest the causative role of age-associated impairments in circadian rhythms on respiratory infections and have clinical relevance.

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