Abstract
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 that Streptococcus pneumoniae pneumolysin (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.
Highlights
Streptococcus pneumoniae is an important pathogen that typically causes otitis media, sinusitis, pneumonia, and more rarely severe infections such as sepsis and meningitis
SUMMARY High-density lipoproteins (HDLs) are a group of different subpopulations of sialylated particles that have an essential role in the reverse cholesterol transport (RCT) pathway
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
Summary
Streptococcus pneumoniae is an important pathogen that typically causes otitis media, sinusitis, pneumonia, and more rarely severe infections such as sepsis and meningitis. Inflammation caused by acute microbial infection or coronary artery disease launches significant changes in lipid metabolism and in the protein and lipid composition of HDL. These chemical, compositional, and structural changes can transform atheroprotective HDL into dysfunctional pro-atherogenic and pro-inflammatory particles with attenuated cholesterol acceptor and anti-inflammatory activities (Pirillo et al, 2015b; Smith, 2010). This suggests a role for microbial molecules in modifying the anti-inflammatory effects of HDL. HDL-2 is more susceptible to oxidation, and the resulting modifications may impair its function in mediating cellular cholesterol efflux (Paavola et al, 2017)
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