Mechanism and implications of CXCR4-mediated integrin activation by Porphyromonas gingivalis

作者：Hajishengallis G^*; McIntosh M L; Nishiyama S I; Yoshimura F

来源：Molecular Oral Microbiology, 2013, 28(4): 239-249.

DOI：10.1111/omi.12021

• CXCR4
• immune evasion
• integrin
• periodontitis
• Porphyromonas gingivalis
• Toll-like receptor 2

In monocytes and macrophages, the interaction of Porphyromonas gingivalis with Toll-like receptor 2 (TLR2) leads to the activation of a MyD88-dependent antimicrobial pathway and a phosphatidylinositol- 3 kinase (PI3K) -dependent pro-adhesive pathway, which activates the b2-integrin complement receptor 3 (CR3). By means of its fimbriae, P. gingivalis binds CXC-chemokine receptor 4 (CXCR4) and induces crosstalk with TLR2 that inhibits the MyD88-dependent antimicrobial pathway. In this paper, we investigated the impact of the P. gingivalis-CXCR4 interaction on the proadhesive pathway. Using human monocytes, mouse macrophages, or receptor-transfected cell lines, we showed that the binding of P. gingivalis fimbriae to CXCR4 induces CR3 activation via PI3K, albeit in a TLR2-independent manner. An isogenic strain of P. gingivalis expressing mutant fimbriae that do not interact with CXCR4 failed to efficiently activate CR3, leading to enhanced susceptibility to killing in vivo compared with the wild-type organism. This in vivo observation is consistent with previous findings that activated CR3 mediates safe entry of P. gingivalis into macrophages. Taken together with our previous work, these results indicate that the interaction of P. gingivalis with CXCR4 leads to inhibition of antimicrobial responses and enhancement of proadhesive responses, thereby maximizing its adaptive fitness in the mammalian host.

• 出版日期2013-8