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Macrophage-Derived IL-1β Regulates Emergency Myelopoiesis via the NF-κB and C/ebpβ in Zebrafish
Zongfang Wei1, Chenzheng Li1, Yangping Zhang2
1Institute of Developmental Biology and Regenerative Medicine, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Southwest University, Chongqing 400715, People's Republic of China.
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 (Danio rerio) 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 il1β 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.
Insights
Macrophages act as early warning signals, initiating emergency myelopoiesis to replenish neutrophils during infection. This process involves interleukin-1 beta (IL1β) signaling and myeloid progenitor response, crucial for immune defense.
Area of Science:
- Immunology
- Hematopoiesis
- Zebrafish models
Background:
- Neutrophils are rapidly depleted during microbial infections, necessitating rapid replenishment.
- Emergency myelopoiesis is essential for maintaining myeloid cell populations but its initiation mechanisms are unclear.
Purpose of the Study:
- To elucidate the cellular and molecular mechanisms initiating emergency myelopoiesis in response to systemic infection.
- To investigate the role of macrophages and myeloid progenitors in this process.
Main Methods:
- Established a systemic infection model in zebrafish larvae using lipopolysaccharide (LPS).
- Analyzed the interaction between macrophages and myeloid progenitors in the caudal hematopoietic tissue.
- Investigated the signaling pathways involved, including IL1β, NF-κB, and C/ebpβ.
Main Results:
- Macrophages were identified as the primary sensors of LPS, initiating an emergency signal via IL1β.
- Myeloid progenitors, not hematopoietic stem cells, responded to the signal.
- Myeloid expansion was driven by the synergistic action of NF-κB and C/ebpβ pathways.
Conclusions:
- Macrophages serve as critical early "whistle blowers" in initiating emergency myelopoiesis.
- The study reveals a specific signaling cascade involving IL1β, NF-κB, and C/ebpβ in myeloid progenitor response.
- This provides new insights into the regulation of innate immune cell production during infection.

