Proteome Analysis of Coinfection of Epithelial Cells with Filifactor alocis and Porphyromonas gingivalis Shows Modulation of Pathogen and Host Regulatory Pathways

Aruni, Wilson; Zhang, Kangling; Dou, Youjun; Fletcher, Hansel M.

doi:10.1128/iai.01727-14

Cited by 37 publications

(47 citation statements)

References 79 publications

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“…Nonetheless, the contribution to disease by these newly appreciated organisms has been overshadowed by the more readily cultivable species, and appreciation of their pathogenicity is just beginning to emerge (8,9). Filifactor alocis is a slow-growing, Gram-positive anaerobe that is consistently found at increased frequency and in elevated numbers at periodontal disease sites compared to healthy sites in culture-independent studies (7,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). In vivo, F. alocis is found in subgingival biofilms (21), and the organism positively correlates with other periodontal pathogens, such as Porphyromonas gingivalis, forming a co-occurrence group that is enriched across different oral habitats (22).…”

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confidence: 99%

Filifactor alocis Promotes Neutrophil Degranulation and Chemotactic Activity

et al. 2016

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Filifactor alocis is a recently recognized periodontal pathogen; however, little is known regarding its interactions with the immune system. As the first-responder phagocytic cells, neutrophils are recruited in large numbers to the periodontal pocket, where they play a crucial role in the innate defense of the periodontium. Thus, in order to colonize, successful periodontal pathogens must devise means to interfere with neutrophil chemotaxis and activation. In this study, we assessed major neutrophil functions, including degranulation and cell migration, associated with the p38 mitogen-activated protein kinase (MAPK) signaling pathway upon challenge with F. alocis. Under conditions lacking a chemotactic gradient, F. alocischallenged neutrophils had increased migration compared to uninfected cells, indicating that F. alocis increases chemokinesis in human neutrophils. In addition, neutrophil chemotaxis induced by interleukin-8 was significantly enhanced when cells were challenged with F. alocis, compared to noninfected cells. Similar to live bacteria, heat-killed F. alocis induced both random and directed migration of human neutrophils. The interaction of F. alocis with Toll-like receptor 2 induced granule exocytosis along with a transient ERK1/2 and sustained p38 MAPK activation. Moreover, F. alocis-induced secretory vesicle and specific granule exocytosis were p38 MAPK dependent. Blocking neutrophil degranulation with TAT-SNAP23 fusion protein significantly reduced the chemotactic and random migration induced by F. alocis. Therefore, we propose that induction of random migration by F. alocis will prolong neutrophil traffic time in the gingival tissue, and subsequent degranulation will contribute to tissue damage.

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confidence: 99%

Filifactor alocis Promotes Neutrophil Degranulation and Chemotactic Activity

et al. 2016

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“…By interacting with other periodontal pathogens, such as Filifactor alocis, a Gram-positive, obligate anaerobic rod bacterium, P. gingivalis plays an important role in infection-induced periodontal disease (12,13). Many epidemiological studies have shown that severe forms of periodontitis are associated with other inflammatory diseases, such as rheumatoid arthritis and cardiovascular disease (14,15).…”

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confidence: 99%

Gingipains from the Periodontal Pathogen Porphyromonas gingivalis Play a Significant Role in Regulation of Angiopoietin 1 and Angiopoietin 2 in Human Aortic Smooth Muscle Cells

et al. 2015

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Angiopoietin 1 (Angpt1) and angiopoietin 2 (Angpt2) are the ligands of tyrosine kinase (Tie) receptors, and they play important roles in vessel formation and the development of inflammatory diseases, such as atherosclerosis. Porphyromonas gingivalis is a Gram-negative periodontal bacterium that is thought to contribute to the progression of cardiovascular disease. The aim of this study was to investigate the role of P. gingivalis infection in the modulation of Angpt1 and Angpt2 in human aortic smooth muscle cells (AoSMCs). We exposed AoSMCs to wild-type (W50 and 381), gingipain mutant (E8 and K1A), and fimbrial mutant (DPG-3 and KRX-178) P. gingivalis strains and to different concentrations of tumor necrosis factor (TNF). The atherosclerosis risk factor TNF was used as a positive control in this study. We found that P. gingivalis (wild type, K1A, DPG3, and KRX178) and TNF upregulated the expression of Angpt2 and its transcription factor ETS1, respectively, in AoSMCs. In contrast, Angpt1 was inhibited by P. gingivalis and TNF. However, the RgpAB mutant E8 had no effect on the expression of Angpt1, Angpt2, or ETS1 in AoSMCs. The results also showed that ETS1 is critical for P. gingivalis induction of Angpt2. Exposure to Angpt2 protein enhanced the migration of AoSMCs but had no effect on proliferation. This study demonstrates that gingipains are crucial to the ability of P. gingivalis to markedly increase the expressed Angpt2/Angpt1 ratio in AoSMCs, which determines the regulatory role of angiopoietins in angiogenesis and their involvement in the development of atherosclerosis. These findings further support the association between periodontitis and cardiovascular disease.

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“…Arginine, which increases the growth of F. alocis in vitro, is abundantly present in periodontal pockets (148). This has been hypothesized to help explain the presence of F. alocis in high numbers in periodontal pockets (149).…”

Section: Filifactor Alocismentioning

confidence: 98%

Tobacco-gene activity profile in Porphyromonas gingivalis, Filifactor alocis and Treponema denticola.

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Proteome Analysis of Coinfection of Epithelial Cells with Filifactor alocis and Porphyromonas gingivalis Shows Modulation of Pathogen and Host Regulatory Pathways

Cited by 37 publications

References 79 publications

Filifactor alocis Promotes Neutrophil Degranulation and Chemotactic Activity

Filifactor alocis Promotes Neutrophil Degranulation and Chemotactic Activity

Gingipains from the Periodontal Pathogen Porphyromonas gingivalis Play a Significant Role in Regulation of Angiopoietin 1 and Angiopoietin 2 in Human Aortic Smooth Muscle Cells

Tobacco-gene activity profile in Porphyromonas gingivalis, Filifactor alocis and Treponema denticola.

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