摘要：SummaryHigh-density lipoproteins (HDLs) are a group of different subpopulations of sialylated particles that have an essential role in the reverse cholesterol transport (RCT) pathway. Importantly, changes in the protein and lipid composition of HDLs may lead to the formation of particles with reduced atheroprotective properties. Here, we show thatStreptococcus pneumoniaepneumolysin (PLY) and neuraminidase A (NanA) impair HDL function by causing chemical and structural modifications of HDLs. The proteomic, lipidomic, cellular, and biochemical analysis revealed that PLY and NanA induce significant changes in sialic acid, protein, and lipid compositions of HDL. The modified HDL particles have reduced cholesterol acceptor potential from activated macrophages, elevated levels of malondialdehyde adducts, and show significantly increased complement activating capacity. These results suggest that accumulation of these modified HDL particles in the arterial intima may present a trigger for complement activation, inflammatory response, and thereby promote atherogenic disease progression.Graphical abstractDisplay OmittedHighlights•S. pneumoniaemolecules PLY and NanA target human high-density lipoprotein (HDL).•These interactions result in major modifications in the HDL proteome and lipidome.•Microbially modified HDL activates humoral and cell-mediated innate immune responses.•The activated immune response mediates formation of pro-atherogenic epitopes on HDL.Cardiovascular medicine; Microbiology
