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 YangJunyan Han, Zhengya Yu, Zhongtao Du, Hong Zheng, Christian Kosan, Ang Li, Chen Chen, Yaluan Ma, Hui Zeng

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Article number113044
JournalCell Reports
Volume42
Issue number9
DOIs
StatePublished - Sep 26 2023

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology

Fingerprint

Dive into the research topics of 'Sepsis induces non-classic innate immune memory in granulocytes'. Together they form a unique fingerprint.

Cite this