Distinct Lipid A Moieties Contribute to Pathogen-Induced Site-Specific Vascular Inflammation

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Several human pathogens express structurally divergent forms of lipid A, the endotoxic portion of lipopolysaccharide (LPS), as a strategy to evade host innate immune detection and establish persistent infection. Expression of modified lipid A species promotes pathogen evasion of host recognition by Toll-like receptor-4 (TLR4) and the non-canonical inflammasome. The Gram-negative oral anaerobe, Porphyromonas gingivalis, expresses lipid A structures that function as TLR4 agonists or antagonists, or are immunologically inert. It is currently unclear how modulation of P. gingivalis lipid A expression contributes to innate immune recognition, survival, and the ability of the pathogen to induce local and systemic inflammation. In this study, we demonstrate that P. gingivalis expression of antagonist lipid A species results in attenuated production of proinflammatory mediators and evasion of non-canonical inflammasome activation, facilitating bacterial survival in the macrophage. Infection of atherosclerosis-prone ApoE−/− mice with this strain resulted in progression of chronic inflammation in the vasculature. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A modifications, supporting distinct mechanisms for induction of local versus systemic inflammation. Our work demonstrates that evasion of immune detection at TLR4 contributes to pathogen persistence and facilitates low-grade chronic inflammation.

Vyšlo v časopise: Distinct Lipid A Moieties Contribute to Pathogen-Induced Site-Specific Vascular Inflammation. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004215
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004215

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