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

Authors :
Hajishengallis, G.
McIntosh, M.L.
Nishiyama, S.‐I.
Yoshimura, F.
Source :
Molecular Oral Microbiology. Aug2013, Vol. 28 Issue 4, p239-249. 11p.
Publication Year :
2013

Abstract

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 β2-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 pro-adhesive 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 pro-adhesive responses, thereby maximizing its adaptive fitness in the mammalian host. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20411006
Volume :
28
Issue :
4
Database :
Academic Search Index
Journal :
Molecular Oral Microbiology
Publication Type :
Academic Journal
Accession number :
88936874
Full Text :
https://doi.org/10.1111/omi.12021