Cell Reports (Sep 2023)
Sepsis induces non-classic innate immune memory in granulocytes
- Beibei Wang,
- Liuluan Zhu,
- Bei Jia,
- Chenchen Zhao,
- Ju Zhang,
- Fangyuan Li,
- Jiarui Li,
- Nan Ding,
- Can Zhang,
- Yu Hao,
- Shuai Tong,
- Jiajia Wang,
- Guoli Li,
- Yang Fan,
- Henghui Zhang,
- Rui Li,
- Juan Du,
- Yaxian Kong,
- Yue Zhang,
- Xiaoyu Yang,
- Junyan Han,
- Zhengya Yu,
- Zhongtao Du,
- Hong Zheng,
- Christian Kosan,
- Ang Li,
- Chen Chen,
- Yaluan Ma,
- Hui Zeng
Affiliations
- Beibei Wang
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China
- Liuluan Zhu
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China
- Bei Jia
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China
- Chenchen Zhao
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China
- Ju Zhang
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China
- Fangyuan Li
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China
- Jiarui Li
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China
- Nan Ding
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China
- Can Zhang
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China
- Yu Hao
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China
- Shuai Tong
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China
- Jiajia Wang
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China
- Guoli Li
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China
- Yang Fan
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China
- Henghui Zhang
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China
- Rui Li
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China
- Juan Du
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China
- Yaxian Kong
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China
- Yue Zhang
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China
- Xiaoyu Yang
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China
- Junyan Han
- Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; Beijing Key Laboratory of Emerging Infectious Diseases, Beijing 100015, China
- Zhengya Yu
- Department of Vascular Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100015, China
- Zhongtao Du
- Department of Vascular Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100015, China
- Hong Zheng
- Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033, USA
- Christian Kosan
- Department of Biochemistry, Center for Molecular Biomedicine (CMB), Friedrich- Schiller-University, 07743 Jena, Germany
- Ang Li
- Intensive Care Unit, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
- Chen Chen
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China
- Yaluan Ma
- The Institute of Basic Medical Theory of Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China; Corresponding author
- Hui Zeng
- Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; Beijing Key Laboratory for Therapeutic Cancer Vaccines, Beijing 100038, China; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 9
p. 113044
Abstract
Summary: 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.
