Document Detail


Chlamydophila pneumoniae phospholipase D (CpPLD) drives Th17 inflammation in human atherosclerosis.
MedLine Citation:
PMID:  22232679     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phospholipases are produced from bacterial pathogens causing very different diseases. One of the most intriguing aspects of phospholipases is their potential to interfere with cellular signaling cascades and to modulate the host-immune response. Here, we investigated the role of the innate and acquired immune responses elicited by Chlamydophila pneumoniae phospholipase D (CpPLD) in the pathogenesis of atherosclerosis. We evaluated the cytokine and chemokine production induced by CpPLD in healthy donors' monocytes and in vivo activated T cells specific for CpPLD that infiltrate atherosclerotic lesions of patients with C. pneumoniae antibodies. We also examined the helper function of CpPLD-specific T cells for monocyte matrix metalloproteinase (MMP)-9 and tissue factor (TF) production as well as the CpPLD-induced chemokine expression by human venular endothelial cells (HUVECs). We report here that CpPLD is a TLR4 agonist able to induce the expression of IL-23, IL-6, IL-1β, TGF-β, and CCL-20 in monocytes, as well as CXCL-9, CCL-20, CCL-4, CCL-2, ICAM-1, and VCAM-1 in HUVECs. Plaque-derived T cells produce IL-17 in response to CpPLD. Moreover, CpPLD-specific CD4(+) T lymphocytes display helper function for monocyte MMP-9 and TF production. CpPLD promotes Th17 cell migration through the induction of chemokine secretion and adhesion molecule expression on endothelial cells. These findings indicate that CpPLD is able to drive the expression of IL-23, IL-6, IL-1β, TGF-β, and CCL-20 by monocytes and to elicit a Th17 immune response that plays a key role in the genesis of atherosclerosis.
Authors:
Marisa Benagiano; Fabio Munari; Alessandra Ciervo; Amedeo Amedei; Silvia Rossi Paccani; Fabiola Mancini; Mauro Ferrari; Chiara Della Bella; Camilla Ulivi; Sofia D'Elios; Cosima T Baldari; Domenico Prisco; Marina de Bernard; Mario M D'Elios
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-09
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-02-06     Completed Date:  2012-03-28     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1222-7     Citation Subset:  IM    
Affiliation:
Patologia Medica, Azienda Ospedaliero-Universitaria Careggi Firenze, 50134 Florence, Italy.
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MeSH Terms
Descriptor/Qualifier:
Aged
Atherosclerosis / immunology*,  microbiology*
Cell Line
Chemokines / immunology
Chlamydophila pneumoniae / enzymology*
Cytokines / immunology
Enzyme-Linked Immunosorbent Assay
Female
Gene Expression Regulation / immunology*
Human Umbilical Vein Endothelial Cells
Humans
Male
Matrix Metalloproteinase 9 / metabolism
Middle Aged
Monocytes / immunology
Phospholipase D / immunology*,  pharmacology
Real-Time Polymerase Chain Reaction
Th17 Cells / immunology*
Thromboplastin / metabolism
Toll-Like Receptor 4 / agonists
Chemical
Reg. No./Substance:
0/Chemokines; 0/Cytokines; 0/TLR4 protein, human; 0/Toll-Like Receptor 4; 9035-58-9/Thromboplastin; EC 3.1.4.4/Phospholipase D; EC 3.4.24.35/Matrix Metalloproteinase 9
Comments/Corrections

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