Study uncovers novel immune evasion mechanism used by key bacterium in periodontitis

Researchers have identified a new mechanism by which a key bacterium in periodontitis evades the immune system. The study reveals that the bacterium exploits the protein CD47 to suppress immune responses, allowing it to persist in inflamed tissues and contribute to systemic diseases. Blocking CD47 or its ligand, thrombospondin-1, could offer a novel strategy for enhancing bacterial clearance and improving periodontal and overall health.

A recent study led by Prof. Gabriel Nussbaum from the Faculty of Dental Medicine at the Hebrew University of Jerusalem has uncovered a novel immune evasion mechanism used by Porphyromonas gingivalis (P. gingivalis), a key bacterial culprit behind periodontitis- a severe gum infection. The study, published in PNAS, sheds light on how this pathogen manipulates the immune system to persist in inflamed oral tissues, increasing risks for systemic diseases like cardiovascular disease, Alzheimer's, and cancer.

The research team found that P. gingivalis exploits the integrin-associated protein CD47 to interfere with the body's immune response. CD47, known as a "don't eat me" signal in cancer cells, plays a crucial role in protecting P. gingivalis from being destroyed by immune cells. Additionally, the study revealed that the bacterium induces the production of thrombospondin-1 (TSP-1), a ligand that further suppresses immune activity, particularly neutrophil-mediated bacterial clearance.

Our findings suggest that P. gingivalis uses CD47 to hijack immune signaling pathways, effectively disabling the host's ability to clear the infection. This mechanism helps explain why this bacterium thrives in inflammatory environments, leading to chronic periodontitis and potentially contributing to other systemic diseases."

Prof. Gabriel Nussbaum, Faculty of Dental Medicine, Hebrew University of Jerusalem

Using both in vitro and in vivo models, the researchers demonstrated that blocking CD47 or TSP-1 significantly enhanced bacterial clearance by the immune system. Mice lacking CD47 showed a higher ability to eliminate P. gingivalis, suggesting that targeting this pathway could provide a promising strategy for treating periodontal disease.

"Current periodontal treatments focus on reducing bacterial load mechanically, but understanding how these bacteria evade immune responses opens new therapeutic possibilities," Prof. Nussbaum added. "Targeting CD47-TLR2 signaling or TSP-1 could represent a novel approach to managing chronic infections linked to oral and systemic health."

Given the strong correlation between periodontitis and conditions such as cardiovascular disease and neurodegenerative disorders, this discovery holds broad implications beyond dentistry. Future research will explore how these findings can translate into clinical therapies aimed at improving immune responses to persistent bacterial infections.