Sepsis induces non-classic innate immune memory in granulocytes

  • Cell Rep. 2023 Aug 28;42(9):113044. doi: 10.1016/j.celrep.2023.113044.
Beibei Wang  1 ,  Liuluan Zhu  1 ,  Bei Jia  1 ,  Chenchen Zhao  1 ,  Ju Zhang  2 ,  Fangyuan Li  2 ,  Jiarui Li  1 ,  Nan Ding  2 ,  Can Zhang  2 ,  Yu Hao  2 ,  Shuai Tong  2 ,  Jiajia Wang  2 ,  Guoli Li  1 ,  Yang Fan  2 ,  Henghui Zhang  2 ,  Rui Li  1 ,  Juan Du  1 ,  Yaxian Kong  1 ,  Yue Zhang  1 ,  Xiaoyu Yang  1 ,  Junyan Han  1 ,  Zhengya Yu  3 ,  Zhongtao Du  3 ,  Hong Zheng  4 ,  Christian Kosan  5 ,  Ang Li  6 ,  Chen Chen  2 ,  Yaluan Ma  7 ,  Hui Zeng  8
Affiliations
  • 1. Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China.
  • 2. Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China.
  • 3. Department of Vascular Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100015, China.
  • 4. Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033, USA.
  • 5. Department of Biochemistry, Center for Molecular Biomedicine (CMB), Friedrich- Schiller-University, 07743 Jena, Germany.
  • 6. Intensive Care Unit, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
  • 7. The Institute of Basic Medical Theory of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: [email protected].
  • 8. Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China. Electronic address: [email protected].
PMID: 37643085 DOI: 10.1016/j.celrep.2023.113044
Abstract

Secondary Infection in patients with sepsis triggers a new wave of inflammatory response, which aggravates organ injury and increases mortality. Trained immunity boosts a potent and nonspecific response to the secondary challenge and has been considered beneficial for the host. Here, using a murine model of polymicrobial Infection, we find that the primary Infection reprograms granulocytes to boost enhanced inflammatory responses to the secondary Infection, including the excessive production of inflammatory cytokines, respiratory burst, and augmented phagocytosis capacity. However, these reprogramed granulocytes exhibit "non-classic" characteristics of innate immune memory. Two mechanisms are independently involved in the innate immune memory of granulocytes: a metabolic shift in favor of glycolysis and fatty acid synthesis and chromatin remodeling leading to the transcriptional inactivity of genes encoding inhibitors of TLR4-initiated signaling pathways. Counteracting the deleterious effects of stressed granulocytes on Anti-infection immunity might provide a strategy to fight secondary infections during sepsis.

Keywords
CP: Immunology; granulocyte; immune memory; secondary infection; sepsis.
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