Circadian regulation of the pulmonary immune response

Circadian clocks are a common feature of life on our planet, allowing physiology and behaviour to be adapted to recurrent environmental fluctuation. In mammals, the circadian timing mechanism is present in most cell types and establishes local cycles of gene expression and metabolic activity. These distributed tissue clocks are normally synchronised by a central pacemaker, the suprachiasmatic nuclei (SCN), located in the hypothalamus. 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. In summary, we identify a surprising gain of anti-bacterial function due to loss of BMAL1 in macrophages, associated with a RhoA dependent cytoskeletal change an increase in cell motility, and gain of phagocytic function.