New study by Gabriel Nussbaum, MD, PhD, et al, reveals how P gingivalis escapes immune detection, contributing to gum disease and increasing risks for systemic infections such as respiratory disease.
Researchers have uncovered how Porphyromonas gingivalis, a bacterium linked to periodontitis, evades immune detection, leading to chronic infections and potentially contributing to serious systemic diseases like cardiovascular disease and Alzheimer’s. This discovery sheds light on the bacterium’s use of the CD47 protein, which sends a “don’t eat me” signal to immune cells, protecting it from being eliminated. Additionally, Pgingivalis induces the production of thrombospondin-1 (TSP-1), which further suppresses immune responses, allowing the bacterium to thrive in inflamed oral tissues.1
The study, led by professor Gabriel Nussbaum, MD, PhD from the Hebrew University of Jerusalem, shows how these immune evasion mechanisms enable P gingivalis to persist, not only contributing to gum disease but also increasing the risk of complications like heart disease and neurodegenerative disorders.
Nussbaum explained that the strategy employed by P gingivalis is not unique to this pathogen. Other oral bacteria also exploit this immune evasion pathway. “Other pathogens from the oral cavity that also thrive in the presence of inflammation also hijack this pathway – we demonstrated a contribution of CD47 and thrombospondin-1 to the survival of Fusobacterium nucleatum and Tannerella forsythia. So this pathway may be shared among ‘inflammophilic’ bacteria associated with periodontitis,” he said.
This finding highlights how inflammation in the mouth can have far-reaching effects. Nussbaum further elaborated on the broader implications of this immune evasion mechanism, “Chronic oral inflammatory diseases such as gum disease may influence these systemic conditions via regulation of systemic inflammatory factors and metabolites. Alternatively, the bacteria that thrive in inflammation may translocate to distant tissues such as atherosclerotic plaque, the brain, tumors, etc, where they can exert local effects. In either case, the mechanisms that enable bacteria such as P gingivalis to achieve higher numbers in the oral cavity are linked to the potential for exerting detrimental systemic effects.”
P gingivalis uses CD47 and thrombospondin-1 to evade immune detection, contributing to chronic infections and systemic disease risks.
Blocking CD47 or TSP-1 improved immune response, suggesting new treatment possibilities for periodontal disease.
The discovery highlights how oral bacteria may affect other parts of the body, including the brain and atherosclerotic plaques.
The researchers’ experiments demonstrated that blocking CD47 or TSP-1 significantly enhanced bacterial clearance by the immune system. Mice lacking CD47 showed a higher capacity to eliminate P gingivalis, suggesting that targeting this immune evasion pathway could provide a promising strategy for treating periodontal disease. Nussbaum highlighted that targeting this pathway could offer a broader solution: “We are exploring various means of interrupting this evasion pathway to improve clinical outcomes, especially since it is shared among pathogens linked to periodontal disease.”
This breakthrough in understanding how P gingivalis and other oral bacteria evade the immune system opens up new avenues for treatment. Nussbaum emphasized that targeting immune evasion mechanisms could not only help control chronic infections like periodontitis but also reduce the risks of systemic diseases linked to these infections. “A deeper understanding of these immune evasion mechanisms can lead to novel ways to reduce the bacterial load of pathogens such as P gingivalis,” he added.
With these insights, researchers are now focused on translating these findings into potential therapies. These could help enhance immune responses and better manage persistent bacterial infections, improving both oral and overall health. As Nussbaum concluded, “Understanding how these bacteria evade immune responses opens new therapeutic possibilities.”
