The Helicobacter cinaedi antigen CAIP participates in atherosclerotic inflammation by promoting the differentiation of macrophages in foam cells

Sci Rep. 2017 Jan 11:7:40515. doi: 10.1038/srep40515.

Abstract

Recent studies have shown that certain specific microbial infections participate in atherosclerosis by inducing inflammation and immune reactions, but how the pathogens implicated in this pathology trigger the host responses remains unknown. In this study we show that Helicobacter cinaedi (Hc) is a human pathogen linked to atherosclerosis development since at least 27% of sera from atherosclerotic patients specifically recognize a protein of the Hc proteome, that we named Cinaedi Atherosclerosis Inflammatory Protein (CAIP) (n = 71). CAIP appears to be implicated in this pathology because atheromatous plaques isolated from atherosclerotic patients are enriched in CAIP-specific T cells (10%) which, in turn, we show to drive a Th1 inflammation, an immunopathological response typically associated to atherosclerosis. Recombinant CAIP promotes the differentiation and maintenance of the pro-inflammatory profile of human macrophages and triggers the formation of foam cells, which are a hallmark of atherosclerosis. This study identifies CAIP as a relevant factor in atherosclerosis inflammation linked to Hc infection and suggests that preventing and eradicating Hc infection could reduce the incidence of atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Bacterial / blood*
  • Antigens, Bacterial / immunology*
  • Atherosclerosis / blood*
  • Atherosclerosis / immunology*
  • Atherosclerosis / microbiology
  • Cell Differentiation*
  • Cell Polarity
  • Chemokines / metabolism
  • Crystallography, X-Ray
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Female
  • Foam Cells / metabolism
  • Foam Cells / pathology*
  • Helicobacter / immunology*
  • Humans
  • Inflammation / blood
  • Inflammation / immunology*
  • Lipoproteins, LDL / metabolism
  • MAP Kinase Signaling System
  • Macrophage Activation
  • Male
  • Middle Aged
  • Models, Molecular
  • Phenotype
  • Plaque, Atherosclerotic / blood
  • Plaque, Atherosclerotic / pathology
  • Receptors, G-Protein-Coupled / metabolism
  • Recombinant Proteins / metabolism
  • Th1 Cells / immunology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Chemokines
  • Lipoproteins, LDL
  • Receptors, G-Protein-Coupled
  • Recombinant Proteins
  • p38 Mitogen-Activated Protein Kinases