Maintaining macrophage homeostasis in the intestine

▸ Bain CC, Bravo-Blas A, Scott CL, et al. Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat Immunol 2014;15:929–37.

Macrophages are essential for pathogen defence, tissue homeostasis and wound repair. The current paradigm that tissue resident macrophages (TRMs) derive from embryonic precursors and are independent of blood monocytes has never been studied in the intestine, which houses the largest pool of TRMs. In this study, the authors set out to investigate the origin of the intestinal TRM compartment in mice from birth until adulthood. Using a combination of immunotyping, lineage tracing and parabiosis techniques, the authors demonstrated that macrophages in the intestine are an exception to this paradigm. Specifically, intestinal macrophages under steady-state conditions are continuously replenished by blood-derived monocytes even though the yolk sac-derived macrophages are seeded to the gut tissue during the neonatal period. Resident intestinal macrophages proliferated in situ in the first few weeks of life, but this lessened concomitantly with the arrival of bone marrow-derived monocytes during weaning, around 2–3 weeks of age. This finding is in stark contrast to results obtained for the liver, lung, spleen, kidney, epidermis and brain, where macrophages retain their embryonic signature into adulthood. The colonic macrophage pool in adult mice was associated with CCR2-dependent recruitment of classic Ly6C^hi monocytes and their subsequent differentiation into mature, anti-inflammatory macrophages. This process was driven mostly by commensal microbiota and continued throughout adulthood to sustain a normal intestinal macrophage pool. This study sheds light on the regulatory mechanisms that control macrophage homeostasis in the highly dynamic intestinal microenvironment. Significant progress has been made into understanding the role of intestinal macrophages in steady-state and inflammatory conditions. In both environments, macrophages of the intestinal wall derive from blood monocytes. From a clinical aspect, future work should …