Tissue surveillance by hematopoietic stem and progenitor cells via microbial-innate immune signal

Systemic infections often shift bone marrow (BM) hematopoiesis towards host defense, but how hematopoietic stem and progenitor cells (HSPCs) sense and integrate the demands of peripheral signals to enhance tissue repari is largely unknown. Here, we show acute gut inflammation permits infiltration of Bacteroides, a gram negative rod, to activate innate immune signaling and expand HSPCs via GM-CSF signaling. Subsequently, HSPCs migrate from the BM to inflamed gut-associated lymph nodes (i.e., MLN) and differentiate into innate immune cells specialized in tissue repair. Similarly, microbial signals contribute to aging-associated expansion of HSPCs in the BM and their accumulation in the MLN. On the contrary, chronic gut inflammation reduces HSC potential for hematopoietic reconstitution and immune-responses to infection by downregulating HSPC lipid metabolism. These findings elucidate the cross-organ communication toward gut tissue repair through microbial signals, and the detrimental effects of chronic inflammatory signals on HSC regulation that may possibly be relevant to aging-associated chronic disorders.