Proteomic Profiling and Functional Analysis of B Cell-Derived Exosomes upon Pneumocystis Infection

Pneumocystis is a life-threatening fungal pathogen frequently causing fatal pneumonia (PCP) in immunocompromised individuals with high mortality. Recently, B cells have been reported to play a crucial role in the pathogenesis of PCP through producing antibodies and activating CD4+ T cell response. Exosomes are nano-scale small extracellular vesicles (EVs) abundant of protein cargo and can mediate immune response during infectious disease. Here, using quantitative proteomic analysis coupled with bioinformatic analysis, we attempted to characterize exosomes derived from B lymphocytes in response to PCP. Also, the effects of B-cell exosomes on CD4+ T cell response and phagocytic function of macrophages were clarified. Briefly, 1701 proteins were identified from B-cell exosomes and the majority of them were reported in Vesiclepedia. 51 differentially expressed proteins of B-cell exosomes were found in response to PCP. They were mainly associated with immune response and transcription regulation. Particularly, a variety of histone components were enriched in B cell-derived exosomes when infected with Pneumocystis. Moreover, functional study revealed the pro-inflammatory profile of B-cell exosomes on CD4+ T cell response in PCP. Taken together, our results suggest the involvement of exosomes derived from B cells in cell-to-cell communication, providing new information on the function of B cells in response to PCP.