Aggregatibacter actinomycetemcomitans induces Th17 cells in atherosclerotic lesions

Th17 cells have been linked to the pathogenesis of several chronic inflammatory and autoimmune diseases. However, the role of Th17 cells and IL-17 in atherosclerosis remains poorly understood. We previously reported that Aggregatibacter actinomycetemcomitans (A alpha) bacteremia accelerated atherosclerosis accompanied by inflammation in apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice. In this study, we investigated whether A alpha promotes the Th17 inducing pathway in A alpha-challenged Apoe(shl) mice. Mice were intravenously injected with live A alpha HK1651 or vehicles. Time-course analysis of splenic IL-17(+) CD4(+) cell frequencies, the proximal aorta lesion area, serum IL-17, IL-6, TGF-beta and IL-1 beta levels, the mRNA expression of Th17-related molecules such as IL-1 beta, IL-6, IL17RA, STAT3, IL-21, IL-23, TGF-beta and ROR gamma t, Th17-related microRNA levels and the levels of AIM-2, Mincle and NLRP3 were examined. Challenge with A alpha time dependently induced tropism of Th17 cells in the spleen and increase in atheromatous lesions in the aortic sinus of Apoe(shl) mice. Serum IL-17, IL-6, TGF-beta and IL-1 beta levels were significantly enhanced by A alpha. The gene expression of IL-1 beta, IL-6, IL-17RA, IL-21, IL-23, TGF-beta, STAT3, ROR gamma t, AIM-2, Mincle and NLRP3 was also time dependently stimulated in the aorta of A alpha-challenged mice. Furthermore, A alpha challenge significantly increased the expression of miR-146b and miR-155 in the aorta. Based on the results, it seems that A alpha stimulates Th17 induction that affects the progression of A alpha-accelerated atherosclerosis.