biostudies-literatureMartelossi Cebinelli GCState of Sao Paulo Research Foundation112083https://www.ebi.ac.uk/biostudies/studies/S-EPMC12003019biostudies-literatureUnknown28(4)The dysregulated host response to infections can lead to sepsis, a complex disease characterized by a spectrum of clinical phenotypes. Using scRNA-seq, we analyzed the immune cell of survived and non-survived CLP-septic mice to gain insights into the immunological mechanisms by which neutrophils contribute to the hyperinflammatory phenotype. Our findings reveal that non-survived mice exhibit increased frequencies of immature CXCR4⁺ PD-L1⁺ neutrophils in the bloodstream, accompanied by an accumulation of trafficking-specific CXCR4⁺ PD-L1⁺ neutrophils into the lungs. The IFN-gamma and LPS promote the PD-L1 expression on neutrophils and an activation profile associated with inflammation and organ damage. Notably, abrogating the IFN-gamma reduced susiScienceCXCR4<sup>+</sup> PD-L1<sup>+</sup> neutrophils are increased in non-survived septic mice.PMC120030192013/08216-22019/15070-0Ramos ADSTavares ACBernardo Nascimento DCAlves Damasceno LEAlves de Lima KAquime Goncalves ANCunha TMImoto Nakaya HTMartelossi Cebinelli GCAlves-Filho JCde Oliveira Leandro Mda Cruz Oliveira Barros CRocha Oliveira AECunha FQDonate PBCosta VfalseCXCR4<sup>+</sup> PD-L1<sup>+</sup> neutrophils are increased in non-survived septic mice.The dysregulated host response to infections can lead to sepsis, a complex disease characterized by a spectrum of clinical phenotypes. Using scRNA-seq, we analyzed the immune cell of survived and non-survived CLP-septic mice to gain insights into the immunological mechanisms by which neutrophils contribute to the hyperinflammatory phenotype. Our findings reveal that non-survived mice exhibit increased frequencies of immature CXCR4⁺ PD-L1⁺ neutrophils in the bloodstream, accompanied by an accumulation of trafficking-specific CXCR4⁺ PD-L1⁺ neutrophils into the lungs. The IFN-gamma and LPS promote the PD-L1 expression on neutrophils and an activation profile associated with inflammation and organ damage. Notably, abrogating the IFN-gamma reduced sus2025-01-01T00:00:00Z2025 Apr2026-06-01T07:52:06.8Z2026-04-08T10:40:26.159ZS-EPMC120030194024176110.1016/j.isci.2025.112083