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Pathogen induction of CXCR4/TLR2 cross-talk impairs host defense function

Hajishengallis, George, Wang, Ming, Liang, Shuang, Triantafilou, Martha ORCID: and Triantafilou, Kathy ORCID: 2008. Pathogen induction of CXCR4/TLR2 cross-talk impairs host defense function. Proceedings of the National Academy of Sciences of the United States of America 105 (36) , pp. 13532-13537. 10.1073/pnas.0803852105

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QR Microbiology > QR180 Immunology
Uncontrolled Keywords: bacterial pathogenesis; immune evasion; macrophages; p. gingivalis; protein kinase A
Publisher: National Academy of Sciences
ISSN: 0027-8424
Last Modified: 19 Oct 2022 10:40

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