CXCR4+ PD-L1+ neutrophils are increased in non-survived septic mice

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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

• Tipo de documento: Artigo Científico
• Fonte: ISCIENCE; v. 28, n. 4, p. 17-pg., 2025-04-18.

Resumo

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)

• Processo FAPESP: 19/15070-0 - Determinação dos mecanismos moleculares e celulares associados com o desfecho da Sepse utilizando a tecnologia de single cell RNA sequencing
• Beneficiário: Guilherme Cesar Martelossi Cebinelli
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs