Role of the P2X7 receptor in intestinal inflammation due to infection with the oral pathogen Porphyromonas gingivalis

Highlights

  • •
    P. gingivalis upregulated P2X7 receptor levels in the colon of wildtype mice.
  • •
    P. gingivalis triggered intestinal inflammation in wildtype mice but not in P2X7-deficient mice.
  • •
    The P. gingivalis-induced liver alterations were reduced in P2X7-deficient mice.
  • •
    P. gingivalis modulates the balance of Treg and Th17 cells in wildtype mice.
  • •
    Oral ingestion of P. gingivalis increases the translocation of gut bacteria to the liver of wildtype mice.


Abstract

Porphyromonas gingivalis (P. gingivalis), a Gram-negative bacterium present in the oral cavity, is one of the primary pathogens associated with periodontitis. P. gingivalis has also been linked to other non-oral pathologies, such as diabetes, colorectal cancer, and inflammatory bowel disease. The P2X7 receptor plays a role in resolving oral infection with P. gingivalis, and, separately, is associated with increased damage in colitis. This study investigated whether ingestion of P. gingivalis could aggravate colitis and whether the P2X7 receptor could play a role in this effect. Wild-type (WT) and P2X7-deficient mice were orally inoculated by gavage with P. gingivalis, and colitis was induced by intrarectal injection with 2,4,6-trinitrobenzene sulfonic acid (TNBS). P. gingivalis ingestion upregulated P2X7 receptor immunoreactivity in the colon of WT mice. P. gingivalis also triggered intestinal inflammation and reduced the colon length in WT mice but not P2X7-deficient mice. The balance of regulatory T (Treg) cells and Th17 cells of the mesenteric lymph node was perturbed in WT mice that had been administered P. gingivalis and TNBS, while this was not observed in P2X7-deficient mice. Th17 cells were increased in WT mice in response to P. gingivalis, while P2X7-deficient mice showed an increase in Treg cells. P. gingivalis ingestion induced liver injury in WT mice, but not in P2X7-deficient mice. Furthermore, the liver from WT mice that had been administered P. gingivalis and TNBS showed higher levels of bacteria than P2X7-deficient mice. Our findings suggest that the P2X7 receptor contributes to the deleterious effects of P. gingivalis on gut inflammation and liver damage.

Read more at:
https://www.sciencedirect.com/science/article/abs/pii/S0024320525006071?via%3Dihub 
https://pubmed.ncbi.nlm.nih.gov/40953801/ 




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