Lipid raft-dependent uptake, signalling and intracellular fate of<i>Porphyromonas gingivalis</i>in mouse macrophages

Wang, Min; Hajishengallis, George

doi:10.1111/j.1462-5822.2008.01185.x

Cited by 68 publications

(58 citation statements)

References 67 publications

(109 reference statements)

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“…However, these inhibitors only minimally affected the binding of the membrane-coated beads and bacteria. Cholesterol depletion by M␤CD suppressed the ability of P. gingivalis for intracellular persistence and cytokine induction in mouse macrophages (33) and abolished actin polymerization induced by P. gingivalis OM vesicles (32). Lipid raft-dependent internalization was also observed with Treponema denticola Mspdeduced peptide conjugate, P34BSA, which induced actin stress fiber formation through PI3K and RhoA activation, although lipid raft activation by P34BSA, but not lipid raft-dependent internalization, is linked to PI3K and RhoA activation (34).…”

Section: Discussionmentioning

confidence: 87%

“…For lipid raft inhibition, we used a concentration for each inhibitor that did not show discernable cytotoxicity in the cells. Lipid raft-dependent internalization of Porphyromonas gingivalis, a representative periodontopathogen, has been also demonstrated in epithelial cells and macrophages (32,33). Lipid raft inhibitors, in particular M␤CD, drastically reduced the internalization of beads coated with the OM vesicles of P. gingivalis in HeLa cells and of P. gingivalis whole bacteria in mouse macrophages.…”

Section: Discussionmentioning

confidence: 92%

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The Major Outer Membrane Protein of a Periodontopathogen Induces IFN-β and IFN-Stimulated Genes in Monocytes via Lipid Raft and TANK-Binding Kinase 1/IFN Regulatory Factor-3

Lee

Kim²,

Jun³

et al. 2009

The Journal of Immunology

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Surface molecules of pathogens play an important role in stimulating host immune responses. Elucidation of the signaling pathways activated by critical surface molecules in host cells provides insight into the molecular pathogenesis resulting from bacteria-host interactions. MspTL is the most abundant outer membrane protein of Treponema lecithinolyticum, which is associated with periodontitis, and induces expression of a variety of proinflammatory factors. Although bacteria and bacterial components like LPS and flagellin are known to induce IFN-β, induction by bacterial surface proteins has not been reported. In the present study, we investigated MspTL-mediated activation of signaling pathways stimulating up-regulation of IFN-β and IFN-stimulated genes in a human monocytic cell line, THP-1 cells, and primary cultured human gingival fibroblasts. MspTL treatment of the cells induced IFN-β and the IFN-stimulated genes IFN-γ-inducible protein-10 (IP-10) and RANTES. A neutralizing anti-IFN-β Ab significantly reduced the expression of IP-10 and RANTES, as well as STAT-1 activation, which was also induced by MspTL. Experiments using specific small interfering RNA showed that MspTL activated TANK-binding kinase 1 (TBK1), but not inducible IκB kinase (IKKi). MspTL also induced dimerization of IFN regulatory factor-3 (IRF-3) and translocation into the nucleus. The lipid rapid-disrupting agents methyl-β-cyclodextrin, nystatin, and filipin inhibited the MspTL internalization and cellular responses, demonstrating that lipid raft activation was a prerequisite for MspTL cellular signaling. Our results demonstrate that MspTL, the major outer protein of T. lecithinolyticum, induced IFN-β expression and subsequent up-regulation of IP-10 and RANTES via TBK1/IRF-3/STAT-1 signaling secondary to lipid raft activation.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 92%

The Major Outer Membrane Protein of a Periodontopathogen Induces IFN-β and IFN-Stimulated Genes in Monocytes via Lipid Raft and TANK-Binding Kinase 1/IFN Regulatory Factor-3

Lee

Kim²,

Jun³

et al. 2009

The Journal of Immunology

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“…P. gingivalis has been shown to induce lipid raft-dependent phagocytosis in macrophages [5]. To invade host cells that are not professional phagocytes, pathogens utilize diverse molecules and strategies.…”

Section: Discussionmentioning

confidence: 99%

“…Porphyromonas gingivalis, a gram-negative anaerobe, is a major colonizer of gingival tissues and has been etiologically implicated in various forms of periodontitis [1]. Cellular invasion by P. gingivalis has been proposed as a possible virulence factor, affording protection from the host immune responses and contributing to tissue damage [2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Differential ability of periodontopathic bacteria to modulate invasion of human gingival epithelial cells by Porphyromonas gingivalis

Saitô

Inagaki

Ishihara

2009

Microbial Pathogenesis

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Periodontitis is a polymicrobial infection caused by selected gram-negative bacteria including Porphyromonas gingivalis. Host cell invasion by P. gingivalis has been proposed as a possible mechanism of pathogenesis in periodontitis. The aim of the present study was to assess the influence of periodontopathogens on P. gingivalis invasion of gingival epithelial cells in polymicrobial infection. P. gingivalis was tested for its ability to invade a human gingival epithelial cell line Ca9-22 in co-infection with periodontopathogens, using an antibiotic protection assay. Among the pathogens tested, only Fusobacterium nucleatum demonstrated the ability to significantly promote P. gingivalis invasion (p < 0.01). This increased invasion was confirmed by confocal scanning laser microscopy utilizing a dual labeling technique. In contrast, co-infection with Aggregatibacter actinomycetemcomitans or Tannerella forsythia attenuated P. gingivalis invasion. The fusobacterial enhancement of host cell invasion was not observed in co-incubation with other periodontopathogens tested.These results suggested that complex synergistic or antagonistic physiologic mechanisms are intimately involved in host cell invasion by P. gingivalis in polymicrobial infection.

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“…Several studies have reported that bacteria utilize lipid rafts or raft-associated molecules for adhesion to or invasion of host cells (11,29,34,59). With H. pylori, previous studies have shown that cholesterol-rich microdomains are required for VacA binding, delivery, and intoxication of cells (20,28,41,48).…”

Section: Discussionmentioning

confidence: 99%

Ceramide and Toll-Like Receptor 4 Are Mobilized into Membrane Rafts in Response to Helicobacter pylori Infection in Gastric Epithelial Cells

Chen

Yang

et al. 2012

Infect Immun

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ABSTRACTHelicobacter pyloriinfection is thought to be involved in the development of several gastric diseases. TwoH. pylorivirulence factors (vacuolating cytotoxin A and cytotoxin-associated gene A) reportedly interact with lipid rafts in gastric epithelial cells. The role of Toll-like receptor (TLR)-mediated signaling in response toH. pyloriinfection has been investigated extensively in host cells. However, the receptor molecules in lipid rafts that are involved inH. pylori-induced innate sensing have not been well characterized. This study investigated whether lipid rafts play a role inH. pylori-induced ceramide secretion and TLR4 expression and thereby contribute to inflammation in gastric epithelial cells. We observed that both TLR4 and MD-2 mRNA and protein levels were significantly higher inH. pylori-infected AGS cells than in mock-infected cells. Moreover, significantly more TLR4 protein was detected in detergent-resistant membranes extracted fromH. pylori-infected AGS cells than in those extracted from mock-infected cells. However, this effect was attenuated by the treatment of cells with cholesterol-usurping agents, suggesting thatH. pylori-induced TLR4 signaling is dependent on cholesterol-rich microdomains. Similarly, the level of cellular ceramide was elevated and ceramide was translocated into lipid rafts afterH. pyloriinfection, leading to interleukin-8 (IL-8) production. Using the sphingomyelinase inhibitor imipramine, we observed thatH. pylori-induced TLR4 expression was ceramide dependent. These results indicate the mobilization of ceramide and TLR4 into lipid rafts byH. pyloriinfection in response to inflammation in gastric epithelial cells.

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Lipid raft-dependent uptake, signalling and intracellular fate ofPorphyromonas gingivalisin mouse macrophages

Cited by 68 publications

References 67 publications

The Major Outer Membrane Protein of a Periodontopathogen Induces IFN-β and IFN-Stimulated Genes in Monocytes via Lipid Raft and TANK-Binding Kinase 1/IFN Regulatory Factor-3

The Major Outer Membrane Protein of a Periodontopathogen Induces IFN-β and IFN-Stimulated Genes in Monocytes via Lipid Raft and TANK-Binding Kinase 1/IFN Regulatory Factor-3

Differential ability of periodontopathic bacteria to modulate invasion of human gingival epithelial cells by Porphyromonas gingivalis

Ceramide and Toll-Like Receptor 4 Are Mobilized into Membrane Rafts in Response to Helicobacter pylori Infection in Gastric Epithelial Cells

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