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Omics · study · 2026

Polymicrobial-driven NLRP6 inflammasome regulates 1 IL-1b production and alveolar bone loss in a murine model of periodontitis

Listed in NCBI GEO

Periodontal disease is a chronic inflammatory condition that develops in response to oral microbiome dysbiosis and host-microbiome immune response dysregulation.

Description

The innate immune system plays a major role in the development and persistence of disease in part by producing inflammatory cytokines. One of the major cytokines implicated in disease is interleukin-1b (IL-1b), which requires inflammasome activation.

Much of the oral microbiome, including Streptococci, which are otherwise considered commensal, is required for the full development of periodontal disease. We have previously reported that inflammatory-activated macrophages and neutrophils counterintuitively allow survival of internalized Streptococcus gordonii over non-activated phagocytes. This internal bacterial survival leads to inflammasome activation via the cytoplasmic activator NLRP6, but not NLRP3, and subsequent increases in IL-1b release.

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Here, we test and find that the keystone pathogen Porphyromonas gingivalis can activate macrophages in a manner that allows for increased S. gordonii survival and IL-1b production above levels when P. gingivalis interacts with macrophages alone. We also use the mouse ligature-induced periodontal disease model to test the importance of NLRP6 in disease development. We found mice lacking NLRP6 had significantly reduced bone loss, IL-1b, and neutrophil infiltration following disease induced by P. gingivalis when S. gordonii or other mouse commensals were present, but had no effect when S. gordonii was inoculated alone.

This work thus reveals an additional important inflammasome activation mechanism by which oral keystone pathogens may stimulate periodontal disease progression.

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From keywords
Life Sciences
Inferred from text
Disease 75%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE33942013 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[disease].local:disease:diseaseenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:10090source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title