GSE210548
Host responses to S. pneumoniae in wild type and Mertk mutant mice I
Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. Mertk is an efferocytosis receptor involved in the recognition and removal of apoptotic debris by macrophages and other phagocytic cells. Here we show that Mertk negatively regulates the clearance of S. pneumoniae, as measured by the greater number of viable bacteria in the lung of wild type vs. Mertk-/- mice 24 hours post-inoculation. The impaired clearance observed in wild type mice was associated with a greater number of neutrophils in the bronchoalveolar lavage (BAL) and lower concentration of IFN? in the BAL fluid; however, similar enhancement of clearance was observed in Mertk-/- mice receiving neutralizing IFN? antibody. Mertk is highly expressed on alveolar macrophages. Transcriptomic changes observed in primary Mertk-/- alveolar macrophages were associated with leukocyte activation, cellular motility, and response to stimulus. Mertk deficiency similarly enhanced proinflammatory gene expression in S. pneumoniae-stimulated alveolar macrophages in vitro and in pneumonic lung tissue. Thus, Mertk contributes to alveolar macrophage homeostasis through the receptor's immunomodulatory role. Naive Mertk-/- alveolar macrophages appear primed for an inflammatory response to S. pneumoniae leading to greater cell motility, improved bacterial killing and enhancement of other innate immune cells through the production of inflammatory mediators. Overall design: Comparative gene expression profiling analysis of RNA-seq data for naive, primary alveolar macrophages isolated from Mertk-/- or wild type mice.