Hajishengallis, George, Wang, Ming, Liang, Shuang, Triantafilou, Martha ![]() ![]() |
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.
Item Type: | Article |
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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 |
URI: | https://orca.cardiff.ac.uk/id/eprint/25172 |
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