| Full text | |
| Author(s): Show less - |
Cebinelli, Guilherme Cesar Martelossi
;
Leandro, Maisa de Oliveira
;
Oliveira, Antonio Edson Rocha
;
de Lima, Kalil Alves
;
Donate, Paula Barbim
;
Barros, Cleyson da Cruz Oliveira
;
Ramos, Anderson dos Santos
;
Costa, Victor
;
Nascimento, Daniele Carvalho Bernardo
;
Damasceno, Luis Eduardo Alves
;
Tavares, Amanda Curto
;
Goncalves, Andre Nicolau Aquime
;
Nakaya, Helder Takashi Imoto
;
Cunha, Thiago Mattar
;
Alves-Filho, Jose Carlos
;
Cunha, Fernando Queiroz
Total Authors: 16
|
| Document type: | Journal article |
| Source: | ISCIENCE; v. 28, n. 4, p. 17-pg., 2025-04-18. |
| Abstract | |
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 susceptibility to CLP-sepsis and diminished CXCR4+ PD-L1+ neutrophils frequency. This study provides insights into the immune cell activation profiles associated with the worsening of the CLP-sepsis, and the CXCR4+ PD-L1+ neutrophils population highlighted here represents a promising target for therapeutic modulation in clinical sepsis hyperinflammatory phenotype. (AU) | |
| FAPESP's process: | 19/15070-0 - Determination of molecular and cellular mechanisms associated with Sepsis outcome using single cell RNA sequencing |
| Grantee: | Guilherme Cesar Martelossi Cebinelli |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 13/08216-2 - CRID - Center for Research in Inflammatory Diseases |
| Grantee: | Fernando de Queiroz Cunha |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |