Hypoxia drives progression of multiple sclerosis by enhancing the inflammasome activation in macrophages with Porphyromonas gingivalis infection
Abstract Porphyromonas gingivalis (Pg), a gram-negative anaerobic bacterium, is a leading pathogen causing periodontitis. It secretes several virulence factors, including gingipains, lipopolysaccharides (LPS), and outer membrane vesicles (OMVs), which can trigger the release of inflammatory cytokine...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-06-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02548-z |
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| Summary: | Abstract Porphyromonas gingivalis (Pg), a gram-negative anaerobic bacterium, is a leading pathogen causing periodontitis. It secretes several virulence factors, including gingipains, lipopolysaccharides (LPS), and outer membrane vesicles (OMVs), which can trigger the release of inflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor alpha (TNFα), and IL-6 through inflammasome activation and Toll-like receptor (TLR) signaling. We demonstrated that Pg infection under hypoxic conditions enhances NLRP3 inflammasome activation in macrophages. Additionally, we observed that toll-interleukin-1 receptor domain-containing adaptor-inducing interferon-β (TRIF)-mediated hypoxia-inducible factor 1 alpha (HIF-1α) regulation exacerbates inflammasome activation under hypoxia. Notably, HIF-1α deficiency in myeloid cells reversed neurological symptoms and reduced IL-1β and IL-17 production in a mouse model of multiple sclerosis with Pg infection. Our findings indicated that hypoxia modulates inflammasome activation in response to periodontitis-related bacterial infections, contributing to the progression of autoimmune diseases. |
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| ISSN: | 2058-7716 |