The mito-DAMP cardiolipin blocks IL-10 production causing persistent inflammation during bacterial pneumonia.

ABSTRACT: Bacterial pneumonia is a significant healthcare burden worldwide. Failure to resolve inflammation after infection precipitates lung injury and an increase in morbidity and mortality. Gram-negative bacteria are common in pneumonia and increased levels of the mito-damage-associated molecular pattern (DAMP) cardiolipin can be detected in the lungs. Here we show that mice infected with Klebsiella pneumoniae develop lung injury with accumulation of cardiolipin. Cardiolipin inhibits resolution of inflammation by suppressing production of anti-inflammatory IL-10 by lung CD11b⁺Ly6G^intLy6C^loF4/80⁺ cells. Cardiolipin induces PPARγ SUMOylation, which causes recruitment of a repressive NCOR/HDAC3 complex to the IL-10 promoter, but not the TNF promoter, there

SUBMITTER: Chakraborty K 

PROVIDER: S-EPMC5241690 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature