title: The Helicobacter cinaedi antigen CAIP participates in atherosclerotic inflammation by promoting the differentiation of macrophages in foam cells.
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.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Mario Milco
authors.initials: MM
authors.lastname: D'Elios
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vallese
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.|Department of Life Sciences, University of Siena, Siena, Italy.
authors.forename: Nagaja
authors.initials: N
authors.lastname: Capitani
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Benagiano
authors.affiliation: Department of Biology and Biotechnology, "C. Darwin", Sapienza University of Rome, Rome, Italy.|Institute Pasteur Italy - Fondazione Cenci Bolognetti, Rome, Italy.
authors.forename: Maria Lina
authors.initials: ML
authors.lastname: Bernardini
authors.affiliation: Department of Food Hygiene and Environmental Health, University of Helsinki, Helsinki, Finland.
authors.forename: Mirko
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Internal Medicine, Department of Medicine-DIMED, University of Padua, Italy.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Rossi
authors.affiliation: Vascular Surgery Unit, Cisanello University Hospital AOUP, Pisa, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Department of Life Sciences, University of Siena, Siena, Italy.
authors.forename: Cosima Tatiana
authors.initials: CT
authors.lastname: Baldari
authors.affiliation: Department of Biomedical Sciences, University of Padua, Padua, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Zanotti
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: de Bernard
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Codolo
mesh_terms: D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology*; D050197:Atherosclerosis / Q000097:blood* / Q000276:immunology* / Q000382:microbiology; D002454:Cell Differentiation; D016764:Cell Polarity; D018925:Chemokines / Q000378:metabolism; D018360:Crystallography, X-Ray; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005487:Foam Cells / Q000378:metabolism / Q000473:pathology*; D016998:Helicobacter / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008262:Macrophage Activation; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D010641:Phenotype; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D018925:Chemokines; D008077:Lipoproteins, LDL; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D048051:p38 Mitogen-Activated Protein Kinases