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 (Aa) bacteremia accelerated atherosclerosis accompanied by inflammation in apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice. In this study, we investigated whether Aa promotes the Th17 inducing pathway in Aa-challenged Apoe(shl) mice. Mice were intravenously injected with live Aa HK1651 or vehicles. Time-course analysis of splenic IL-17(+)CD4(+) cell frequencies, the proximal aorta lesion area, serum IL-17, IL-6, TGF-β and IL-1β levels, the mRNA expression of Th17-related molecules such as IL-1β, IL-6, IL17RA, STAT3, IL-21, IL-23, TGF-β and RORγt, Th17-related microRNA levels and the levels of AIM-2, Mincle and NLRP3 were examined. Challenge with Aa 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-β and IL-1β levels were significantly enhanced by Aa. The gene expression of IL-1β, IL-6, IL-17RA, IL-21, IL-23, TGF-β, STAT3, RORγt, AIM-2, Mincle and NLRP3 was also time dependently stimulated in the aorta of Aa-challenged mice. Furthermore, Aa challenge significantly increased the expression of miR-146b and miR-155 in the aorta. Based on the results, it seems that Aa stimulates Th17 induction that affects the progression of Aa-accelerated atherosclerosis.
Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Matsudo-shi, Chiba 271-8587, Japan Stomatology Hospital, Tongji University, Shanghai, China.
Ru
R
Jia
Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Matsudo-shi, Chiba 271-8587, Japan.
Tomomi
T
Hashizume-Takizawa
Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Matsudo-shi, Chiba 271-8587, Japan Department of Stomatology, College of Tianjin Medical University, Tianjin, China.
Yuan
Y
Du
Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Matsudo-shi, Chiba 271-8587, Japan.
Masafumi
M
Yamamoto
Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Matsudo-shi, Chiba 271-8587, Japan ochiai.tomoko@nihon-u.ac.jp.
Tomoko
T
Kurita-Ochiai
D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D000818:Animals; D050197:Atherosclerosis / Q000382:microbiology* / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling; D051379:Mice; D013154:Spleen / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
D016207:Cytokines
Aggregatibacter actinomycetemcomitans; Th17 cells; atherosclerosis; inflammasome; microRNA