Microbiota, Immune Subversion, and Chronic Inflammation
| Autor: | Carolyn D. Kramer, Caroline A. Genco |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mini Review Immunology Inflammation immune subversion Biology medicine.disease_cause Systemic inflammation Microbiology Lipid A 03 medical and health sciences Immune system immune dysregulation Immunopathology medicine microbiota Immunology and Allergy Porphyromonas gingivalis innate immunity Innate immune system Immune dysregulation biology.organism_classification 3. Good health 030104 developmental biology toll-like receptors inflammation medicine.symptom atherosclerosis |
| Zdroj: | Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2017.00255 |
| Popis: | Several host-adapted pathogens and commensals have evolved mechanisms to evade the host innate immune system inducing a state of low-grade inflammation. Epidemiological studies have also documented the association of a subset of these microorganisms with chronic inflammatory disorders. In this review, we summarize recent studies demonstrating the role of the microbiota in chronic inflammatory diseases and discuss how specific microorganisms subvert or inhibit protective signaling normally induced by toll-like receptors (TLRs). We highlight our work on the oral pathogen Porphyromonas gingivalis and discuss the role of microbial modulation of lipid A structures in evasion of TLR4 signaling and resulting systemic immunopathology associated with atherosclerosis. P. gingivalis intrinsically expresses underacylated lipid A moieties and can modify the phosphorylation of lipid A, leading to altered TLR4 signaling. Using P. gingivalis mutant strains expressing distinct lipid A moieties, we demonstrated that expression of antagonist lipid A was associated with P. gingivalis-mediated systemic inflammation and immunopathology, whereas strains expressing agonist lipid A exhibited modest systemic inflammation. Likewise, mice deficient in TLR4 were more susceptible to vascular inflammation after oral infection with P. gingivalis wild-type strain compared to mice possessing functional TLR4. Collectively, our studies support a role for P. gingivalis-mediated dysregulation of innate and adaptive responses resulting in immunopathology and systemic inflammation. We propose that anti-TLR4 interventions must be designed with caution, given the balance between the protective and destructive roles of TLR signaling in response to microbiota and associated immunopathologies. |
| Databáze: | OpenAIRE |
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