Mouse, but Not Human, ApoB-100 Lipoprotein Cholesterol Is a Potent Innate Inhibitor of Pneumolysin

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The pore-forming cholesterol-dependent cytolysins (CDCs) are one of the most widely disseminated virulence factors expressed by Gram-positive pathogens. Streptococcus pneumoniae is a major human pathogen and expresses a CDC termed pneumolysin (PLY). PLY and most CDCs bind cholesterol as their cellular receptor, which initiates the formation of the oligomeric pore complex. Our studies show the cholesterol carried by mouse ApoB-100 (CH-ApoB-100), but not human or guinea pig ApoB-100 lipoproteins, acts as a potent innate PLY inhibitor. This selective inhibitory capacity is not due to differences in CH-ApoB-100 levels, but appears to result from differences in cholesterol presentation at the surface of the ApoB-100 particle from these species. Our results suggest bacterial pathogenesis studies of S. pneumoniae and other CDC-producing bacteria utilizing mouse animal models may not reflect the CDCs true contribution to human disease or the potential efficacy of CDC-based vaccines due to the innate potent CDC inhibitory activity of mouse CH-ApoB-100.

Vyšlo v časopise: Mouse, but Not Human, ApoB-100 Lipoprotein Cholesterol Is a Potent Innate Inhibitor of Pneumolysin. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004353
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004353

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