Blocking HXA₃-mediated neutrophil elastase release during <i>S. pneumoniae</i> lung infection limits pulmonary epithelial barrier disruption and bacteremia.

ABSTRACT: Streptococcus pneumoniae (Sp), a leading cause of community-acquired pneumonia, can spread from the lung into the bloodstream to cause septicemia and meningitis, with a concomitant threefold increase in mortality. Limitations in vaccine efficacy and a rise in antimicrobial resistance have spurred searches for host-directed therapies that target pathogenic immune processes. Polymorphonuclear leukocytes (PMNs) are essential for infection control but can also promote tissue damage and pathogen spread. The major Sp virulence factor, pneumolysin, triggers acute inflammation by stimulating the 12-lipoxygenase (12-LOX) eicosanoid synthesis pathway in epithelial cells. This pathway is required for systemic spread in a mouse pneumonia model and produces a number of bioactive li

SUBMITTER: Xu S 

PROVIDER: S-EPMC11389395 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature