Proteomic profiling of serum small extracellular vesicles reveals immune signatures of children with pneumonia

Background: Pneumonia is the leading cause of death in young children globally. However, the underlying pathological mechanism of pediatric pneumonia remains unclear. In infection disease contexts, small extracellular vesicles (sEVs) have been shown to be a useful source of markers for pathogenesis and immune response. We hypothesized that functional molecules such as protein harbored by sEVs would provide mechanistic insights into the immune response in children with pneumonia. Methods: We isolated sEVs from serum collected from children with and without pneumonia, performed proteomic analysis of the sEVs with label-free mass spectrometry, and then conducted functional enrichment analysis of proteomic data. Results: We identified fifteen differentially expressed proteins and ten unique proteins in children with pneumonia as compared to healthy children. In the pneumonia group, immune-related processes and pathways were positively enriched as upregulated proteins were involved in neutrophil activation, complement regulation, defense against bacteria, humoral immune response and regulation of immune effector processes However, pathways associated with tissue development and extracellular matrix remodeling were negatively enriched, as downregulated proteins were linked to extracellular matrix structure and cell adhesions. Conclusions: Our findings provided insights into host responses to pathogen infection, which has contributed to understanding the pathogenesis of children with pneumonia. Furthermore, our studies suggested that serum sEVs proteins could be considered a potential source of biomarkers for diagnosing pediatric pneumonia.