Macrophage-Derived IL-1β Regulates Emergency Myelopoiesis via the NF-κB and C/ebpβ in Zebrafish

Abstract

Myeloid phagocytes, neutrophils in particular, are easily consumed when they fight against a large number of invading microbes. Hence, they require efficient and constant replenishment from their progenitors via the well-orchestrated emergency myelopoiesis in the hematopoietic organs. The cellular and molecular details of the danger-sensing and warning processes to activate the emergency myelopoiesis are still under debate. In this study, we set up a systemic infection model in zebrafish (<i>Danio rerio</i>) larvae via circulative administration of LPS. We focused on the cross-talk of macrophages with myeloid progenitors in the caudal hematopoietic tissue. We revealed that macrophages first detected LPS and sent out the emergency message via <i>il1β</i> The myeloid progenitors, rather than hematopoietic stem and progenitor cells, responded and fulfilled the demand to adapt myeloid expansion through the synergistic cooperation of NF-κB and C/ebpβ. Our study unveiled a critical role of macrophages as the early "whistle blowers" to initiate emergency myelopoiesis.