Gut-resident macrophages represent a highly heterogenous population. In Cell, Mucida and colleagues use imaging and transcriptional profiling to demonstrate specialization of two macrophage populations with distinct localization in the intestinal tissue. Lamina propria macrophages tend to express genes encoding pro-inflammatory (M1) factors, while muscularis macrophages, located under the mucosal region, between the circular and longitudinal muscle layers, express genes encoding tissue-protective factors, such as Il10, Mrc1 and Rentla, and, overall, resemble M2 macrophages. After intragastric exposure of mice to non-invasive Salmonella typhimurium, muscularis macrophages further upregulate M2-associated genes, while lamina propria macrophages increase their expression of Nos2 and Il6. Muscularis macrophages have high expression of genes encoding β2 adrenergic receptors and during infection respond to norepinephrine by upregulating Arg1. Thus, communication between sympathetic neurons and muscularis macrophages induces a tissue-protective program.

Cell (14 January 2016) doi:10.1016/j.cell.2015.12.023