Heart Care Info - Heart Disease Prevention & Treatment

Chlamydophila pneumoniae phospholipase D (CpPLD) drives Th17 inflammation in human atherosclerosis

M Benagiano, F Munari, A Ciervo... - Proceedings of the ..., 2012 - National Acad Sciences Abstract 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 hostimmune response. Here, we ...

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 (Cp PLD) in the pathogenesis of atherosclerosis. We evaluated the cytokine and chemokine production induced by Cp PLD in healthy donors’ monocytes and in vivo activated T cells specific for Cp PLD that infiltrate atherosclerotic lesions of patients with C. pneumoniae antibodies. We also examined the helper function of Cp PLD-specific T cells for monocyte matrix metalloproteinase (MMP)-9 and tissue factor (TF) production as well as the Cp PLD-induced chemokine expression by human venular endothelial cells (HUVE Cs). We report here that Cp PLD 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 HUVE Cs. Plaque-derived T cells produce IL-17 in response to Cp PLD. Moreover, Cp PLD-specific CD4+ T lymphocytes display helper function for monocyte MMP-9 and TF production. Cp PLD promotes Th17 cell migration through the induction of chemokine secretion and adhesion molecule expression on endothelial cells. These findings indicate that Cp PLD 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.