TY - JOUR T1 - Microbiota regulates the turnover kinetics of gut macrophages in health and inflammation JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101178 VL - 5 IS - 1 SP - e202101178 AU - Qi Chen AU - Sajith Nair AU - Christiane Ruedl Y1 - 2022/01/01 UR - https://www.life-science-alliance.org/content/5/1/e202101178.abstract N2 - The gut immune system has evolved to co-exist in a mutually beneficial symbiotic relationship with its microflora. Here, using a germ-free fate-mapping mouse model, we provide clear insight into how the enteric commensals determine the kinetics of macrophage turnover. The microbiome density along the gastrointestinal tract defines the persistence of ontogenically diverse macrophages, with the highest numbers of the long-lived F4/80hiTim4+ macrophage subset in the less densely colonized small intestine. Furthermore, the microbiome contributes to a tightly regulated monocyte-dependent replenishment of both long- and short-lived F4/80hi macrophages under homeostatic and inflammatory conditions. In the latter situation, the commensals regulate rapid replenishment of the depleted macrophage niche caused by the intestinal inflammation. The microbial ecosystem imprints a favorable cytokine microenvironment in the intestine to support macrophage survival and monocyte-dependent replenishment. Therefore, the host immune system-commensal cross-talk provides an efficient strategy to assure intestinal homeostasis. ER -