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.

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.