title: Pathogen induction of CXCR4/TLR2 cross-talk impairs host defense function.
abstract: We report a mechanism of microbial evasion of Toll-like receptor (TLR)-mediated immunity that depends on CXCR4 exploitation. Specifically, the oral/systemic pathogen Porphyromonas gingivalis induces cross-talk between CXCR4 and TLR2 in human monocytes or mouse macrophages and undermines host defense. This is accomplished through its surface fimbriae, which induce CXCR4/TLR2 co-association in lipid rafts and interact with both receptors: Binding to CXCR4 induces cAMP-dependent protein kinase A (PKA) signaling, which in turn inhibits TLR2-mediated proinflammatory and antimicrobial responses to the pathogen. This outcome enables P. gingivalis to resist clearance in vitro and in vivo and thus to promote its adaptive fitness. However, a specific CXCR4 antagonist abrogates this immune evasion mechanism and offers a promising counterstrategy for the control of P. gingivalis periodontal or systemic infections.
authors.affiliation: Division of Oral Health and Systemic Disease/Department of Periodontics, University of Louisville Health Sciences Center, Louisville, KY 40292, USA.
authors.forename: George
authors.initials: G
authors.lastname: Hajishengallis
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.forename: Martha
authors.initials: M
authors.lastname: Triantafilou
authors.forename: Kathy
authors.initials: K
authors.lastname: Triantafilou