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  3. Single-Cell Landscape of Bronchoalveolar Lavage Fluid Identifies Specific Neutrophils during Septic Immunosuppression

Single-Cell Landscape of Bronchoalveolar Lavage Fluid Identifies Specific Neutrophils during Septic Immunosuppression

  • Adv Sci (Weinh). 2025 Jan 30:e2406218. doi: 10.1002/advs.202406218.
Rong Shen 1 2,  Yi Jiang 3 4,  Guanglong Liu 1 2,  Shenjia Gao 3 4,  Hao Sun 3 4,  Xinyi Wu 3 4,  Jiahui Gu 3 4,  Han Wu 3 4,  Ke Mo 5,  Xing Niu 5,  Ronen Ben-Ami 6,  Wanjing Shang 7,  Jie Zhang 3 4,  Jun Wang 8,  Changhong Miao 3 4,  Zhizhang Wang 1 2,  Wankun Chen 3 4 9 10
Affiliations

Affiliations

  • 1 Department of Pathology, Nanfang Hospital, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
  • 2 Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, 510515, China.
  • 3 Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
  • 4 Shanghai Key laboratory of Perioperative Stress and Protection, Shanghai, 200032, China.
  • 5 Experimental Center of BIOQGene, YuanDong International Academy Of Life Sciences, Hong Kong, 999077, China.
  • 6 Infectious Diseases Unit, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, 6997801, Israel.
  • 7 Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, 20814, USA.
  • 8 Department of Integrative Medicine and Neurobiology, School of Basic Medical Science, Institutes of Integrative Medicine, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
  • 9 Department of Anesthesiology, Shanghai Geriatric Medical Center, Shanghai, 201104, China.
  • 10 Department of Anesthesiology, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201700, China.
PMID: 39887584 DOI: 10.1002/advs.202406218
Abstract

Sepsis-induced immunosuppression is related to increased susceptibility to secondary infections and death. Lung is the most vulnerable target organ in sepsis, but the understanding of the pulmonary immunosuppression state is still limited. Here, single-cell RNA Sequencing of bronchoalveolar lavage fluid (BALF) is performed to map the landscape of immune cells, revealing a neutrophil-driven immunosuppressive program in the lungs of patients with immunosuppressive sepsis. Although immunosuppressive genes are upregulated in different immune cells, only neutrophils dramatically increase in the BALF of patients in immunosuppressive phase of sepsis. Five neutrophil subpopulations in BALF are identified, among which CXCR2+ and CD274 (PD-L1 coding gene)+IL1RN+ neutrophil subpopulations increased significantly during septic immunosuppression. Interestingly, a developmental trajectory from CXCR2+ to CD274+IL1RN+ neutrophil subpopulation is disclosed. Moreover, the therapeutic effect of CXCR2 blockade is observed on the survival of septic mice, along with a decreased number of PD-L1+ neutrophils. Taken together, the CXCR2+ neutrophil subpopulation is discovered as a contributor to immunosuppression in sepsis and identified it as a potential therapeutic target in sepsis treatment.

Keywords

CXCR2; bronchoalveolar lavage fluid; neutrophils; sepsis; single‐cell RNA sequencing.

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