Exosomal secreted SCIMP regulates communication between macrophages and neutrophils in pneumonia

• Published in: Nature communications 2024-01, Vol.15 (1), p.691-17, Article 691
• Main Authors: Pei, Xiaolei, Liu, Li, Wang, Jieru, Guo, Changyuan, Li, Qingqing, Li, Jia, Ren, Qian, Ma, Runzhi, Zheng, Yi, Zhang, Yan, Zheng, Danfeng, Wang, Pingzhang, Jiang, Ping, Feng, Xiaoming, Jiang, Erlie, Wang, Ying, Feng, Sizhou
• Format: Article
• Language: English
• Subjects: 13/1; 13/109; 13/31; 13/51; 14/19; 14/28; 631/250/2499; 631/250/262; 631/250/98; 64/60; 82/81; Acute Lung Injury; Adaptor proteins; Adaptor Proteins, Signal Transducing; Animals; Antagonists; Blood cells; Bronchus; Cell activation; Chemotactic response; Chemotaxis; Communication; Exosomes; Genome, Human; Genomes; Humanities and Social Sciences; Humans; Immune clearance; Immune response; Inflammation; Lavage; Leukocytes (neutrophilic); Macrophages; Membrane proteins; Membranes; Mice; multidisciplinary; Neutrophils; Pathogens; Peptides; Perfusion; Peripheral blood; Pneumonia; Proteins; Science; Science (multidisciplinary); Suppressors; Survival
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-44714-4

In pneumonia, the deficient or delayed pathogen clearance can lead to pathogen proliferation and subsequent overactive immune responses, inducing acute lung injury (ALI). While screening human genome coding genes using our peripheral blood cell chemotactic platform, we unexpectedly find SLP adaptor and CSK interacting membrane protein (SCIMP), a protein with neutrophil chemotactic activity secreted during ALI. However, the specific role of SCIMP in ALI remains unclear. In this study, we investigate the secretion of SCIMP in exosomes (SCIMP exo ) by macrophages after bacterial stimulation, both in vitro and in vivo. We observe a significant increase in the levels of SCIMP exo in bronchoalveolar lavage fluid and serum of pneumonia patients. We also find that bronchial perfusion with SCIMP exo or SCIMP N-terminal peptides increases the survival rate of the ALI model. This occurs due to the chemoattraction and activation of peripheral neutrophils dependent on formyl peptide receptor 1/2 (FPR1/2). Conversely, exosome suppressors and FPR1/2 antagonists decrease the survival rate in the lethal ALI model. Scimp -deficient and Fpr1/2 -deficient mice also have lower survival rates and shorter survival times than wild-type mice. However, bronchial perfusion of SCIMP rescues Scimp -deficient mice but not Fpr1/2 -deficient mice. Collectively, our findings suggest that the macrophage-SCIMP-FPRs-neutrophil axis plays a vital role in the innate immune process underlying ALI. In this work, authors report on SCIMP-positive exosomes secreted by macrophages, that play a crucial anti-inflammatory role in pneumonia. Exosomal SCIMP primarily achieves bacterial clearance by the SCIMP-FPRs-neutrophils chemotaxis.