CXCR4+ PD-L1+ 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<sup>+</sup> PD-L1<sup>+</sup> neutrophils in the bloodstream, accompanied by an accumulation of trafficking-specific CXCR4<sup>+</sup> PD-L1<sup>+</sup> 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<sup>+</sup> PD-L1<sup>+</sup> neutrophils frequency. This study provides insights into the immune cell activation profiles associated with the worsening of the CLP-sepsis, and the CXCR4<sup>+</sup> PD-L1<sup>+</sup> neutrophils population highlighted here represents a promising target for therapeutic modulation in clinical sepsis hyperinflammatory phenotype.
Authors
- José C. Alves‐Filho (ORCID: https://orcid.org/0000-0002-9918-8714)
- Kalil Alves de Lima (ORCID: https://orcid.org/0000-0002-9149-168X)
- Luis Eduardo Alves Damasceno (ORCID: https://orcid.org/0000-0003-2833-9244)
- Helder I. Nakaya (ORCID: https://orcid.org/0000-0001-5297-9108)
- Victor Ferreira Costa (ORCID: https://orcid.org/0000-0003-4484-7660)
- Fernando Q. Cunha (ORCID: https://orcid.org/0000-0003-4755-1670)
- Guilherme Cesar Martelossi Cebinelli (ORCID: https://orcid.org/0000-0001-7593-1035)
- Daniele C. Nascimento (ORCID: https://orcid.org/0000-0002-0620-339X)
- Antônio Edson Rocha Oliveira (ORCID: https://orcid.org/0000-0001-8783-9009)
- Anderson dos Santos Ramos (ORCID: https://orcid.org/0000-0002-3487-7914)
- Paula B. Donate (ORCID: https://orcid.org/0000-0001-8422-8894)
- Ana Helena Tavares (ORCID: https://orcid.org/0000-0003-4632-3561)
- Maria Leandro (ORCID: https://orcid.org/0000-0002-2254-4610)
- André N. A. Gonçalves (ORCID: https://orcid.org/0000-0001-5264-8368)
- Thiago Mattar Cunha (ORCID: https://orcid.org/0000-0002-7855-3700)
- Cleyson da Cruz Oliveira Barros (ORCID: https://orcid.org/0000-0002-8541-6544)
Institutions
- Universidade de São Paulo (BR)
- Hospital Israelita Albert Einstein (BR)
- Universidade de Fortaleza (BR)
Publication Details
- Journal
- iScience
- Published
- 2025-02-22
- DOI
- https://doi.org/10.1016/j.isci.2025.112083
- Citations
- 3
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 2.39
Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo