TLR2/CXCR4 coassociation facilitates Chlamydia pneumoniae infection-induced atherosclerosis.

Chlamydia pneumoniae infection could play a role in atherosclerosis. Toll-like receptor 2 (TLR2) and C-X-C motif chemokine receptor 4 (CXCR4) have been both shown to be involved in atherosclerosis. However, whether and how TLR2/CXCR4 cross talk is involved in C. pneumoniae infection-induced atherosclerosis remains to be determined. Our study aims to demonstrate that C. pneumoniae infection induced the cross talk between TLR2 and CXCR4 to mediate C. pneumoniae infection-induced vascular smooth muscle cell (VSMC) migration and even accelerate atherosclerosis. We first found that C. pneumoniae infection increased the aortic lesion size (en face), cross-sectional lesion area, and lipid content in aortic root lesion, which were both significantly reduced in apolipoprotein E-null (ApoE-/-)TLR2-/- or CXCR4-blocked ApoE-/- mice and were almost reversed in CXCR4-blocked ApoE-/-TLR2-/- mice. Subsequently, our data showed that C. pneumoniae infection-induced increases in VSMC contents in the atherosclerotic lesion were remarkably suppressed in ApoE-/-TLR2-/- mice or CXCR4-blocked ApoE-/- mice, and were further decreased in CXCR4-blocked ApoE-/-TLR2-/- mice. We then demonstrated that the increase in VSMC migratory capacity caused by C. pneumoniae infection was inhibited by either TLR2 or CXCR4 depletion, and downregulating both TLR2 and CXCR4 further decreased C. pneumoniae infection-induced VSMC migration by suppressing the infection-stimulated F-actin reorganization through the inhibition of the phosphorylation of focal adhesion kinase. Taken together, our data indicate that TLR2/CXCR4 coassociation facilitates C. pneumoniae infection-induced acceleration of atherosclerosis by inducing VSMC migration via focal adhesion kinase-mediated F-actin reorganization.NEW & NOTEWORTHY Toll-like receptor 2 (TLR2) and C-X-C motif chemokine receptor 4 (CXCR4) have both been shown to be involved in atherosclerosis. We demonstrate for the first time the presence of TLR2/CXCR4 coassociation during Chlamydia pneumoniae infection-induced atherosclerosis. Amazingly, blocking of both TLR2 and CXCR4 significantly retards and even almost reverses this infection-induced atherosclerosis. Our work reveals new mechanisms about C. pneumoniae infection-induced atherosclerosis and identifies potential new therapeutic targets for the prevention and treatment of atherosclerosis.