Identification and characterization of neutrophil heterogeneity in sepsis

• DOI: 10.1186/s13054-021-03481-0
• Publication Date: 2021-02-08T18:37:11Z
• Authors: Xinxin Qi; Yao Yu; Ran Sun; Jiamin Huang; Lu Liu; Yunxi Yang; Tao Rui; Bingwei Sun
• Keywords: Infiltration (HVAC)

Abstract Background Although the immune function of neutrophils in sepsis has been well described, heterogeneity remains unclear during process sepsis. Methods In this study, we used a mouse CLP model to simulate clinical scenario patients with sepsis, neutrophil infiltration, abnormal distribution and dysfunction was analyzed. LPS stimulate vitro sepsis; single-cell gene sequencing technology explore immunological typing. To immunosuppressive neutrophils, PD-L1 knockout were cocultured lymphocytes from wild-type mice. Results We found that presented variant at late stage including inhibition apoptosis, seriously damaged chemotaxis extensive infiltration into tissues. Single-cell RNA revealed multiple subclusters differentiated after stimulation. The two-dimensional spatial analysis showed Foxp3 + T cells much closer Ly-6G than CD4 CD8 cells, indicating infiltrated may play immunomodulatory effect on surrounding T-regs. Further observations mediates over expression through p38α-MSK1/-MK2 pathway neutrophils. subsets highly expressed exert under direct contact mode, cell activation induction apoptosis trans-differentiation. Conclusions Taken together, our data identify previously unknown subset as inhibitory order more accurately describe phenotype characteristics these