Association between Porphyromonas Gingivalis and systemic diseases: Focus on T cells-mediated adaptive immunity

Abstract

The association between periodontal disease and systemic disease has become a research hotspot. Porphyromonas gingivalis (P. gingivalis), a crucial periodontal pathogen, affects the development of systemic diseases. The pathogenicity of P. gingivalis is largely linked to interference with the host's immunity. This review aims to discover the role of P. gingivalis in the modulation of the host's adaptive immune system through a large number of virulence factors and the manipulation of cellular immunological responses (mainly mediated by T cells). These factors may affect the cause of large numbers of systemic diseases, such as atherosclerosis, hypertension, adverse pregnancy outcomes, inflammatory bowel disease, diabetes mellitus, non-alcoholic fatty liver disease, rheumatoid arthritis, and Alzheimer's disease. The point of view of adaptive immunity may provide a new idea for treating periodontitis and related systemic diseases.

Keywords: Porphyromonas gingivalis; adaptive immune response; adverse pregnancy outcomes; atherosclerosis; inflammatory bowel disease; periodontal diseases; rheumatoid arthritis; systemic diseases.

Figure 1

This figure aims to display the presumed contribution of P. gingivalis to atherosclerosis via the regulation of the adaptive immune system. The figure shows a diagram of an open blood vessel affected by atherosclerotic plaque. Within the diagram, we can see that there are different types of immune cells affected in the blood vessels and atherosclerotic plaques. As infection rises within the blood vessels caused by P. gingivalis, the Th17/Treg cell population becomes imbalanced (an increase in the Th17 cell population and a decrease in the Treg cell population) and reduces TGF-β1 levels. In reaction to P. gingivalis, AP-1 transcription factor activity was reduced. The accumulation of IL-2 is influenced by P. gingivalis and partially affects the suppression of AP-1, which affects Treg proliferation. The involvement of adaptive immune responses of the host is proven by the evidence of increased anti-Pg lgG and anti-Pg hsp60 lgG. (Created with BioRender.com).

Figure 2

In this diagram, P. gingivalis infection displays a series of activities and effects that lead to bone and cartilage damage. The infection activates proteases and peptidylarginine deiminase (PPADs), which generates citrullinated proteins and triggers the synthesis of anti-citrullinated protein antibodies (ACPAs). In the above reaction, antigen presenting cells (APC) can not only activate T cells and promote B cells’ autoantibodies production, but also produce inflammatory cytokines (such as IL-6, IL-23, IL-1β) to induce Th17 cells, which also affect the development of RA. With the combination of the inflammatory process stimulated by macrophages, dendritic cells (DCs), and T cells, the host response towards citrullinated proteins occurs. With this response, immune cells begin to produce proinflammatory mediators such as interleukins (ILs), prostaglandins (PGs), tumour necrosis factor (TNF), and metalloproteinases (MMPs). The mediators mentioned above also contribute to the irritation of immune responses. IL-17, an important cytokine of Th17 cells, induces osteoblast expression of receptor activator of the factor nuclear kappa B ligand (RANKL), which stimulates osteoclast activation. Enhanced expression of rheumatoid factor (RF) and ACPAs is caused by a resultant signal against citrullinated epitopes in the joints, and such enhanced expression then aids in the formation of immune complexes. These immune complexes form to empower the host’s inflammatory development, which may further complicate RA. Furthermore, ACPAs, RF and other autoantibodies (such as antibodies against carbamylated proteins (anti-CarP), anti-acetylated protein antibodies (AAPA)) may also contribute to the inflammatory process by activating osteoclasts directly and resulting in bone and cartilage damage. (Created with BioRender.com).