The clock gene <i>Bmal1</i> inhibits macrophage motility, phagocytosis, and impairs defense against pneumonia.

ABSTRACT: The circadian clock regulates many aspects of immunity. Bacterial infections are affected by time of day, but the mechanisms involved remain undefined. Here we show that loss of the core clock protein BMAL1 in macrophages confers protection against pneumococcal pneumonia. Infected mice show both reduced weight loss and lower bacterial burden in circulating blood. In vivo studies of macrophage phagocytosis reveal increased bacterial ingestion following Bmal1 deletion, which was also seen in vitro. BMAL1^-/- macrophages exhibited marked differences in actin cytoskeletal organization, a phosphoproteome enriched for cytoskeletal changes, with reduced phosphocofilin and increased active RhoA. Further analysis of the BMAL1^-/- macrophages identified altered cell morpho

SUBMITTER: Kitchen GB 

PROVIDER: S-EPMC6983378 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature