Signaling events in pathogen-induced macrophage foam cell formation

Pathog Dis. 2016 Aug;74(6):ftw074. doi: 10.1093/femspd/ftw074. Epub 2016 Jul 31.

Abstract

Macrophage foam cell formation is a key event in atherosclerosis. Several triggers induce low-density lipoprotein (LDL) uptake by macrophages to create foam cells, including infections with Porphyromonas gingivalis and Chlamydia pneumoniae, two pathogens that have been linked to atherosclerosis. While gene regulation during foam cell formation has been examined, comparative investigations to identify shared and specific pathogen-elicited molecular events relevant to foam cell formation are not well documented. We infected mouse bone marrow-derived macrophages with P. gingivalis or C. pneumoniae in the presence of LDL to induce foam cell formation, and examined gene expression using an atherosclerosis pathway targeted plate array. We found over 30 genes were significantly induced in response to both pathogens, including PPAR family members that are broadly important in atherosclerosis and matrix remodeling genes that may play a role in plaque development and stability. Six genes mainly involved in lipid transport were significantly downregulated. The response overall was remarkably similar and few genes were regulated in a pathogen-specific manner. Despite very divergent lifestyles, P. gingivalis and C. pneumoniae activate similar gene expression profiles during foam cell formation that may ultimately serve as targets for modulating infection-elicited foam cell burden, and progression of atherosclerosis.

Keywords: Chlamydia pneumoniae; Porphyromonas gingivalis; atherosclerosis; foam cell; innate immunity; macrophage.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Chlamydophila pneumoniae / immunology
  • Cluster Analysis
  • Computational Biology / methods
  • Cytokines / metabolism
  • Foam Cells / immunology
  • Foam Cells / metabolism*
  • Foam Cells / microbiology
  • Foam Cells / pathology*
  • Gene Expression Profiling
  • Gene Ontology
  • Host-Pathogen Interactions* / genetics
  • Host-Pathogen Interactions* / immunology
  • Immunity, Innate
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / microbiology
  • Inflammation Mediators / metabolism
  • Lipid Metabolism
  • Lipid Peroxidation
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / microbiology
  • Macrophages / pathology*
  • Mice
  • Molecular Sequence Annotation
  • Porphyromonas gingivalis / immunology
  • Signal Transduction*

Substances

  • Cytokines
  • Inflammation Mediators