Oral Pathogen Porphyromonas gingivalis Can Escape Phagocytosis of Mammalian Macrophages

Abstract

Macrophages are phagocytic cells that play a key role in host immune response and clearance of microbial pathogens. Porphyromonas gingivalis is an oral pathogen associated with the development of periodontitis. Escape from macrophage phagocytosis was tested by infecting THP-1-derived human macrophages and RAW 264.7 mouse macrophages with strains of P. gingivalis W83 and 33277 as well as Streptococcus gordonii DL1 and Escherichia coli OP50 at MOI = 100. CFU counts for all intracellular bacteria were determined. Then, infected macrophages were cultured in media without antibiotics to allow for escape and escaping bacteria were quantified by CFU counting. P. gingivalis W83 displayed over 60% of the bacterial escape from the total amount of intracellular CFUs, significantly higher compared to all other bacteria strains. In addition, bacterial escape and re-entry were also tested and P. gingivalis W83, once again, showed the highest numbers of CFUs able to exit and re-enter macrophages. Lastly, the function of the PG0717 gene of P. gingivalis W83 was tested on escape but found not related to this activity. Altogether, our results suggest that P. gingivalis W83 is able to significantly avoid macrophage phagocytosis. We propose this ability is likely linked to the chronic nature of periodontitis.

Porphyromonas gingivalis regulates atherosclerosis through an immune pathway

“…It was found that P. gingivalis can undergo repeated cycling behavior in and out of cells in macrophages and successfully avoid macrophage killing ( 143 ), which may be related to the following mechanisms. First, the high heme concentration in the inflammatory environment can convert P. gingivalis surface lipid A to a tetraacylated form without TLR4 agonistic activity, limiting macrophage activation ( 144 – 146 ).…”

“…Systemic dissemination can occur after P. gingivalis has successfully entered the bloodstream and evaded host immune killing. There are four ways for P. gingivalis to disseminate with the blood circulation: first, it is planktonic; second, it binds to the CR1 immune adhesion receptor on the erythrocyte membrane ( 180 ); third, it binds to the SIGN receptor on DCs and enters the DCs and survives intracellularly ( 181 ); fourth, it survives in macrophages and can enter and exit the cells repeatedly ( 143 ). P. gingivalis in the oral cavity can follow the above four ways to reach the AS lesion site ( Figure 2 ).…”

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

“…Firstly, the capsule of P. gingivalis is able to reduce the ability of macrophage to phagocytose P. gingivalis , and the hemagglutinin/adhesion domain of gingipains can cleave the LPS receptor CD14 from the surface of macrophages, resulted in a lower ability to phagocytize bacteria ( 89 , 90 ). When phagocytosed by macrophages, P. gingivalis is able to exit macrophages therefor avoiding being killed ( 91 ). Besides, P. gingivalis utilizes the complement C5a receptor 1-toll-like receptor 2 (C5aR1-TLR2) pathway to subvert immune response and suppresses phagolysosomal maturation, thus promotes intracellular survival ( 15 ).…”

“…Once TLR2 is activated, P. gingivalis initiates downstream phosphatidylinositol 3-kinase (PI3K) instead of myeloid differentiation factor 88 (MyD88)signaling pathway to escape immune clearance, TLR2- PI3K signaling suppressing the phagolysosomal maturation thereby escaping intracellular killing in macrophages ( 93 ). An in vitro experiment also demonstrated that P. gingivalis displayed a significant cycle of entering, exiting, and re-entering in macrophages to avoid being killed ( 91 ), implicating that low abundance of P. gingivalis may still induce severe tissue damage. Gingival tissues from healthy individuals and those with periodontitis contain sphingolipids (SLs), an amphipathic lipid that is essential for P. gingivalis to survive under oxidative stress.…”

Classifying Integrated Signature Molecules in Macrophages of Rheumatoid Arthritis, Osteoarthritis, and Periodontal Disease: An Omics-Based Study

“…In general, macrophages are polarized into pro-inflammatory macrophages (M1) and anti-inflammatory macrophages (M2) based on the type of cytokines and phenotypes they produce. In certain studies, disease development has been linked to abnormal M1 and M2 polarization [ 23 , 24 ]. In the oral environment, macrophages adopt an M1 phenotype during the acute phase of inflammation (chronic PD condition) to eradicate invading pathogens and then transition to M2, which increases migration and immunosuppression activity [ 25 ].…”