Macrophages: A communication network linking Porphyromonas gingivalis infection and associated systemic diseases

Abstract

Porphyromonas gingivalis (P. gingivalis) is a Gram-negative anaerobic pathogen that is involved in the pathogenesis of periodontitis and systemic diseases. P. gingivalis has recently been detected in rheumatoid arthritis (RA), cardiovascular disease, and tumors, as well as Alzheimer’s disease (AD), and the presence of P. gingivalis in these diseases are correlated with poor prognosis. Macrophages are major innate immune cells which modulate immune responses against pathogens, however, multiple bacteria have evolved abilities to evade or even subvert the macrophages’ immune response, in which subsequently promote the diseases’ initiation and progression. P. gingivalis as a keystone pathogen of periodontitis has received increasing attention for the onset and development of systemic diseases. P. gingivalis induces macrophage polarization and inflammasome activation. It also causes immune response evasion which plays important roles in promoting inflammatory diseases, autoimmune diseases, and tumor development. In this review, we summarize recent discoveries on the interaction of P. gingivalis and macrophages in relevant disease development and progression, such as periodontitis, atherosclerosis, RA, AD, and cancers, aiming to provide an in-depth mechanistic understanding of this interaction and potential therapeutic strategies.

Multifunctionalized and Dual‐Crosslinked Hydrogel Promotes Inflammation Resolution and Bone Regeneration via NLRP3 Inhibition in Periodontitis

“…Macrophage polarization manifests various functions in anti‐infection and inflammation regulation because the balance between pro‐ (M1) and anti‐inflammatory (M2) macrophages is crucial for maintaining periodontal homeostasis. [ 4 ] Nonetheless, chronic and uncontrollable infection results in prolonged M1 polarization instead of M2 polarization of macrophages, suggesting a delayed transition from the anti‐infection to the anti‐inflammation stage. This could lead to the failure of tissue reconstruction.…”

“…Accumulative evidence has shown the importance of macrophages in defending periodontal infection and launching regeneration. [4,36] Host inflammation responds to bacterial invasion; however, sustained and chronic infection results in uncontrollable inflammatory effects that could compromise periodontal homeostasis. [31,37] Pathogens like P. gingivalis pull the danger alarm as pathogen-associated molecular patterns (PAMPs), which induce the pyroptosis of macrophages via NLRP3 inflammasome activation.…”

“…The elimination of pathogens is aided by the macrophagemediated inflammatory response, but the concurrent production of reactive oxygen species (ROS) and proinflammatory cytokines aggravates tissue destruction. [4,5] Furthermore, evidences from both clinical and experimental studiesindicate that IL-1β and IL-18 are significantly expressed during periodontitis. These cytokines are considered to dominate the potential connection between periodontitis and cardiovascular diseases or other systemic diseases by rapidly recruiting immunocytes and promoting subsequent tissue damage.…”

A biomimetic phototherapeutic nanoagent based on bacterial double-layered membrane vesicles for comprehensive treatment of oral squamous cell carcinoma

“…Besides promoting the maturation of DCs, LPS is also known to stimulate the M1 polarization of macrophages, which will facilitate remodeling the antitumor immune microenvironment. 42,43 The results shown in Fig. 2B revealed that DMVs from attenuated Pg and PBAE/IR780@DMV both contained approximately 50% of the LPS content of DMVs from Pg.…”

Porphyromonas gingivalis regulates atherosclerosis through an immune pathway

“…P. gingivalis , which survives in macrophages, induces inflammatory vesicle activation and M1-type polarization in macrophages ( 155 ). Animal studies have shown that oral inoculation of P. gingivalis can activate NLRP3 inflammasomes in macrophages in AS plaques in a gingipains-independent manner, promote the release of IL-1β and TNF-α, and accelerate AS progression ( 47 , 148 ).…”