Porphyromonas gingivalis Exacerbates Ligature-Induced, RANKL-Dependent Alveolar Bone Resorption via Differential Regulation of Toll-Like Receptor 2 (TLR2) and TLR4

ABSTRACTToll-like receptors (TLRs) play a key role in the innate immune responses to periodontal pathogens in periodontal disease. The present study was performed to determine the roles of TLR2 and TLR4 signaling in alveolar bone resorption, using aPorphyromonas gingivalis-associated ligature-induced periodontitis model in mice. Wild-type (WT), Tlr2−/−, and Tlr4−/−mice (8 to 10 weeks old) in the C57/BL6 background were used. Silk ligatures were applied to the maxillary second molars in the presence or absence of liveP. gingivalisinfection. Ligatures were removed from the second molars on day 14, and mice were kept for another 2 weeks before sacrifice for final analysis (day 28). On day 14, there were no differences in alveolar bone resorption and gingival RANKL expression between mice treated with ligation plusP. gingivalisinfection and mice treated with ligation alone. Gingival interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) expression was increased, whereas IL-10 expression was decreased in WT and Tlr2−/−mice but not in Tlr4−/−mice. On day 28, WT and Tlr4−/−mice treated with ligation plusP. gingivalisinfection showed significantly increased bone loss and gingival RANKL expression compared to those treated with ligation alone, whereas such an increase was diminished in Tlr2−/−mice. Gingival TNF-α upregulation and IL-10 downregulation were observed only in WT and Tlr4−/−mice, not in Tlr2−/−mice. In all mice, bone resorption induced by ligation plusP. gingivalisinfection was antagonized by local anti-RANKL antibody administration. This study suggests thatP. gingivalisexacerbates ligature-induced, RANKL-dependent periodontal bone resorption via differential regulation of TLR2 and TLR4 signaling.

Download Full-text

E-Selectin Mediates Porphyromonas gingivalis Adherence to Human Endothelial Cells

Infection and Immunity ◽

10.1128/iai.06098-11 ◽

2012 ◽

Vol 80 (7) ◽

pp. 2570-2576 ◽

Cited By ~ 16

Author(s):

Toshinori Komatsu ◽

Keiji Nagano ◽

Shinsuke Sugiura ◽

Makoto Hagiwara ◽

Naomi Tanigawa ◽

...

Keyword(s):

Endothelial Cells ◽

Porphyromonas Gingivalis ◽

Umbilical Vein ◽

Vascular Inflammation ◽

Periodontal Pathogen ◽

Sialyl Lewis X ◽

Necrosis Factor Alpha ◽

Content Type ◽

Tnf Α ◽

Umbilical Vein Endothelial Cells

ABSTRACTPorphyromonas gingivalis, a major periodontal pathogen, may contribute to atherogenesis and other inflammatory cardiovascular diseases. However, little is known about interactions betweenP. gingivalisand endothelial cells. E-selectin is a membrane protein on endothelial cells that initiates recruitment of leukocytes to inflamed tissue, and it may also play a role in pathogen attachment. In the present study, we examined the role of E-selectin inP. gingivalisadherence to endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor alpha (TNF-α) to induce E-selectin expression. Adherence ofP. gingivalisto HUVECs was measured by fluorescence microscopy. TNF-α increased adherence of wild-typeP. gingivalisto HUVECs. Antibodies to E-selectin and sialyl Lewis X suppressedP. gingivalisadherence to stimulated HUVECs.P. gingivalismutants lacking OmpA-like proteins Pgm6 and -7 had reduced adherence to stimulated HUVECs, but fimbria-deficient mutants were not affected. E-selectin-mediatedP. gingivalisadherence activated endothelial exocytosis. These results suggest that the interaction between host E-selectin and pathogen Pgm6/7 mediatesP. gingivalisadherence to endothelial cells and may trigger vascular inflammation.

Download Full-text

Porphyromonas gingivalis Lipopolysaccharide Weakly Activates M1 and M2 Polarized Mouse Macrophages but Induces Inflammatory Cytokines

Infection and Immunity ◽

10.1128/iai.02325-14 ◽

2014 ◽

Vol 82 (10) ◽

pp. 4190-4203 ◽

Cited By ~ 47

Author(s):

James A. Holden ◽

Troy J. Attard ◽

Katrina M. Laughton ◽

Ashley Mansell ◽

Neil M. O'Brien-Simpson ◽

...

Keyword(s):

Nitric Oxide ◽

Porphyromonas Gingivalis ◽

Inflammatory Cytokines ◽

Interleukin 4 ◽

High Dose ◽

Necrosis Factor Alpha ◽

Content Type ◽

Murine Bone Marrow ◽

Whole Cells ◽

Tnf Α

ABSTRACTPorphyromonas gingivalisis associated with chronic periodontitis, an inflammatory disease of the tooth's supporting tissues. Macrophages are important in chronic inflammatory conditions, infiltrating tissue and becoming polarized to an M1 or M2 phenotype. As responses to stimuli differ between these phenotypes, we investigated the effect ofP. gingivalislipopolysaccharide (LPS) on M1 and M2 macrophages. M1 and M2 polarized macrophages were produced from murine bone marrow macrophages (BMMϕ) primed with gamma interferon (IFN-γ) or interleukin-4 (IL-4), respectively, and incubated with a low or high dose ofP. gingivalisLPS or control TLR2 and TLR4 ligands. In M1-Mϕ, the high dose ofP. gingivalisLPS (10 μg/ml) significantly increased the expression of CD40, CD86, inducible nitric oxide synthase, and nitric oxide secretion. The low dose ofP. gingivalisLPS (10 ng/ml) did not induce costimulatory or antibacterial molecules but did increase the secretion of IL-1α, IL-6, IL-12p40, IL-12p70, and tumor necrosis factor alpha (TNF-α).P. gingivalisLPS marginally increased the expression of CD206 and YM-1, but it did enhance arginase expression by M2-Mϕ. Furthermore, the secretion of the chemokines KC, RANTES, eotaxin, and MCP-1 from M1, M2, and nonpolarized Mϕ was enhanced byP. gingivalisLPS. TLR2/4 knockout macrophages combined with the TLR activation assays indicated that TLR2 is the main activating receptor forP. gingivalisLPS and whole cells. In conclusion, althoughP. gingivalisLPS weakly activated M1-Mϕ or M2-Mϕ compared to control TLR ligands, it induced the secretion of inflammatory cytokines, particularly TNF-α from M1-Mϕ and IL-10 from M2-Mϕ, as well as chemotactic chemokines from polarized macrophages.

Download Full-text

Porphyromonas gulae Has Virulence and Immunological Characteristics Similar to Those of the Human Periodontal Pathogen Porphyromonas gingivalis

Infection and Immunity ◽

10.1128/iai.01500-15 ◽

2016 ◽

Vol 84 (9) ◽

pp. 2575-2585 ◽

Cited By ~ 17

Author(s):

Jason C. Lenzo ◽

Neil M. O'Brien-Simpson ◽

Rebecca K. Orth ◽

Helen L. Mitchell ◽

Stuart G. Dashper ◽

...

Keyword(s):

Bone Resorption ◽

Proteolytic Activity ◽

Porphyromonas Gingivalis ◽

Alveolar Bone ◽

Companion Animals ◽

Active Species ◽

Periodontal Pathogen ◽

Content Type ◽

Oral Epithelial Cells ◽

Genes Encoding

Periodontitis is a significant problem in companion animals, and yet little is known about the disease-associated microbiota. A major virulence factor for the human periodontal pathogenPorphyromonas gingivalisis the lysyl- and arginyl-specific proteolytic activity of the gingipains. We screened severalPorphyromonasspecies isolated from companion animals—P. asaccharolytica,P. circumdentaria,P. endodontalis,P. levii,P. gulae,P. macacae,P. catoniae, andP. salivosa—for Lys- and Arg-specific proteolytic activity and compared the epithelial and macrophage responses and induction of alveolar bone resorption of the protease active species to that ofPorphyromonas gingivalis. OnlyP. gulaeexhibited Lys-and Arg-specific proteolytic activity. The genes encoding the gingipains (RgpA/B and Kgp) were identified in theP. gulaestrain ATCC 51700 and all publicly available 12 draft genomes ofP. gulaestrains.P. gulaeATCC 51700 induced levels of alveolar bone resorption in an animal model of periodontitis similar to those inP. gingivalisW50 and exhibited a higher capacity for autoaggregation and binding to oral epithelial cells with induction of apoptosis. Macrophages (RAW 264.7) were found to phagocytoseP. gulaeATCC 51700 and the fimbriatedP. gingivalisATCC 33277 at similar levels. In response toP. gulaeATCC 51700, macrophages secreted higher levels of cytokines than those induced byP. gingivalisATCC 33277 but lower than those induced byP. gingivalisW50, except for the interleukin-6 response. Our results indicate thatP. gulaeexhibits virulence characteristics similar to those of the human periodontal pathogenP. gingivalisand therefore may play a key role in the development of periodontitis in companion animals.

Download Full-text

Reduction of Articular and Systemic Inflammation by Kava-241 in a Porphyromonas gingivalis-Induced Arthritis Murine Model

Infection and Immunity ◽

10.1128/iai.00356-18 ◽

2018 ◽

Vol 86 (9) ◽

Cited By ~ 10

Author(s):

Olivier Huck ◽

Jian You ◽

Xianxian Han ◽

Bin Cai ◽

James Panek ◽

...

Keyword(s):

Porphyromonas Gingivalis ◽

Murine Model ◽

Joint Inflammation ◽

Inflammatory Cells ◽

Mitogen Activated Protein Kinase ◽

Necrosis Factor Alpha ◽

Content Type ◽

Inflammatory Conditions ◽

Inflammatory Score ◽

Tnf Α

ABSTRACT Rheumatoid arthritis (RA) is an inflammatory disease that has been linked to several risk factors, including periodontitis. Identification of new anti-inflammatory compounds to treat arthritis is needed. We had previously demonstrated the beneficial effect of Kava-241, a kavain-derived compound, in the management of Porphyromonas gingivalis-induced periodontitis. The present study evaluated systemic and articular effects of Kava-241 in an infective arthritis murine model triggered by P. gingivalis bacterial inoculation and primed with a collagen antibody cocktail (CIA) to induce joint inflammation and tissular destruction. Clinical inflammation score and radiological analyses of the paws were performed continuously, while histological assessment was obtained at sacrifice. Mice exposed to P. gingivalis and a CIA cocktail and treated concomitantly with Kava-241 exhibited a reduced clinical inflammatory score and a decreased number of inflammatory cells and osteoclasts within joint. Kava-241 treatment also decreased significantly tumor necrosis factor alpha (TNF-α) in serum from mice injected with a Toll-like receptor 2 or 4 (TLR-2/4) ligand, P. gingivalis-lipopolysaccharide (LPS). Finally, bone marrow-derived macrophages infected with P. gingivalis and exposed to Kava-241 displayed reduced TLR-2/4, reduced mitogen-activated protein kinase (MAPK)-related signal elements, and reduced LPS-induced TNF-α factor (LITAF), all explaining the observed reduction of TNF-α secretion. Taken together, these results emphasized the novel properties of Kava-241 in the management of inflammatory conditions, especially TNF-α-related diseases such as infective RA.

Download Full-text

Effect of Angiotensin II Receptor Blocker on Experimental Periodontitis in a Mouse Model of Marfan Syndrome

Infection and Immunity ◽

10.1128/iai.00886-12 ◽

2012 ◽

Vol 81 (1) ◽

pp. 182-188 ◽

Cited By ~ 15

Author(s):

Naoto Suda ◽

Keiji Moriyama ◽

Ganjargal Ganburged

Keyword(s):

Angiotensin Ii ◽

Bone Resorption ◽

Mouse Model ◽

Marfan Syndrome ◽

Alveolar Bone ◽

Wild Type ◽

Angiotensin Ii Receptor ◽

Content Type ◽

Severe Periodontitis ◽

Tnf Α

Marfan syndrome is an autosomal dominant disease characterized by aneurysm and dilatation of the aortic root, tall stature, and ectopia lentis. These manifestations reflect excessive signaling of transforming growth factor beta (TGF-β). Moreover, cases are frequently associated with severe periodontitis, which is a chronic inflammation of the gingiva, periodontal ligament, and alveolar bone. Recently, angiotensin II receptor blockers (ARBs) were discovered to be an effective drug class that can prevent aortic aneurysm and dilation in Marfan syndrome by inhibiting TGF-β signaling. To investigate the effect of ARB on the progression of periodontitis, the application of a potent ARB, telmisartan, was examined in a mouse model of Marfan syndrome (MgΔ). Six-week-old male heterozygous MgΔ and wild-type mice were challenged withPorphyromonas gingivalis, which causes chronic periodontitis, with and without telmisartan application. After infection, alveolar bone resorption was measured by micro-computed tomography (μCT), and inflammatory cytokine levels were examined. Infection ofPorphyromonas gingivalisinduced alveolar bone resorption in both MgΔ and wild-type mice. The amount of resorption was significantly larger in the former than the latter. Immunoarray and enzyme-linked immunosorbent assay (ELISA) analyses demonstrated that interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α) levels were significantly higher in infected MgΔ mice than infected wild-type mice. Telmisartan treatment significantly suppressed the alveolar bone resorption of infected MgΔ mice. Telmisartan also significantly decreased levels of TGF-β, IL-17, and TNF-α in infected MgΔ mice to levels seen in infected wild-type mice. This study suggests that ARB can prevent the severe periodontitis frequently seen in Marfan syndrome.

Download Full-text

Identification and Characterization of MicroRNA Differentially Expressed in Macrophages Exposed to Porphyromonas gingivalis Infection

Infection and Immunity ◽

10.1128/iai.00771-16 ◽

2017 ◽

Vol 85 (3) ◽

Cited By ~ 24

Author(s):

Olivier Huck ◽

Jacob Al-Hashemi ◽

Laetitia Poidevin ◽

Olivier Poch ◽

Jean-Luc Davideau ◽

...

Keyword(s):

Porphyromonas Gingivalis ◽

Osteoclast Differentiation ◽

Bioinformatic Analysis ◽

Innate Immune ◽

Inflammatory Factor ◽

Calvarial Bone ◽

Necrosis Factor Alpha ◽

Content Type ◽

Tnf Α

ABSTRACT MicroRNAs (miRNAs) are short, noncoding RNAs involved in the regulation of several processes associated with inflammatory diseases and infection. Bacterial infection modulates miRNA expression to subvert any innate immune response. In this study we analyzed, using microarray analysis, the bacterial modulation of miRNAs in bone marrow-derived macrophages (BMMs) in which activity was induced by infection with Porphyromonas gingivalis. The expression of several miRNAs was modulated 3 h postinfection (at a multiplicity of infection of 25). A bioinformatic analysis was performed to further identify pathways related to the innate immune host response under the influence of selected miRNAs. To assess the effects of the miRNAs identified on cytokine secretion (tumor necrosis factor alpha [TNF-α] and interleukin-10 [IL-10]), BMMs were transfected with selected miRNA mimics and inhibitors. Transfection with mmu-miR-155 and mmu-miR-2137 did not modify TNF-α secretion, while their inhibitors increased it. Inhibitors of mmu-miR-2137 and mmu-miR-7674 increased the secretion of the anti-inflammatory factor IL-10. In P. gingivalis-infected BMMs, mmu-miR-155-5p significantly decreased TNF-α secretion while inhibitor of mmu-miR-2137 increased IL-10 secretion. In vivo, in a mouse model of P. gingivalis-induced calvarial bone resorption, injection of mmu-miR-155-5p or anti-mmu-miR-2137 reduced the size of the lesion significantly. Furthermore, anti-mmu-miR-2137 significantly reduced inflammatory cell infiltration, osteoclast activity, and bone loss. Bioinformatic analysis demonstrated that pathways related to cytokine- and chemokine-related pathways but also osteoclast differentiation may be involved in the effects observed. This study contributes further to our understanding of P. gingivalis-induced modulation of miRNAs and their physiological effects. It highlights the potential therapeutic merits of targeting mmu-miR-155-5p and mmu-miR-2137 to control inflammation induced by P. gingivalis infection.

Download Full-text

Febuxostat Attenuates the Progression of Periodontitis in Rats

Pharmacology ◽

10.1159/000513034 ◽

2021 ◽

pp. 1-11

Author(s):

Naseratun Nessa ◽

Miyuki Kobara ◽

Hiroe Toba ◽

Tetsuya Adachi ◽

Toshiro Yamamoto ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Pressure ◽

Bone Resorption ◽

Alveolar Bone ◽

Alveolar Bone Loss ◽

Gingival Tissue ◽

Systemic Effects ◽

Rt Pcr ◽

Tnf Α ◽

And Oxidative Stress

Introduction: Periodontitis is a lifestyle-related disease that is characterized by chronic inflammation in gingival tissue. Febuxostat, a xanthine oxidase inhibitor, exerts anti-inflammatory and antioxidant effects. Objective: The present study investigated the effects of febuxostat on periodontitis in a rat model. Methods: Male Wistar rats were divided into 3 groups: control, periodontitis, and febuxostat-treated periodontitis groups. Periodontitis was induced by placing a ligature wire around the 2nd maxillary molar and the administration of febuxostat (5 mg/kg/day) was then initiated. After 4 weeks, alveolar bone loss was assessed by micro-computed tomography and methylene blue staining. The expression of osteoprotegerin (OPG), a bone resorption inhibitor, was detected by quantitative RT-PCR and immunological staining, and the number of osteoclasts in gingival tissue was assessed by tartrate-resistant acid phosphatase staining. The mRNA and protein expression levels of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), in gingival tissue were measured using quantitative RT-PCR and immunological staining. Oxidative stress in gingival tissue was evaluated by the expression of 4-hydroxy-2-nonenal (4-HNE), and 8-hydroxy-2-deoxyguanosine (8-OHdG). To clarify the systemic effects of periodontitis, blood pressure and glucose tolerance were examined. Results: In rats with periodontitis, alveolar bone resorption was associated with reductions in OPG and increases in osteoclast numbers. The gingival expression of TNF-α, IL-1β, 4-HNE, and 8-OHdG was up-regulated in rats with periodontitis. Febuxostat significantly reduced alveolar bone loss, proinflammatory cytokine levels, and oxidative stress. It also attenuated periodontitis-induced glucose intolerance and blood pressure elevations. Conclusion: Febuxostat prevented the progression of periodontitis and associated systemic effects by inhibiting proinflammatory mediators and oxidative stress.

Download Full-text

Changes in Antigen-Specific Cytokine and Chemokine Responses to Plasmodium falciparum Antigens in a Highland Area of Kenya after a Prolonged Absence of Malaria Exposure

Infection and Immunity ◽

10.1128/iai.01924-14 ◽

2014 ◽

Vol 82 (9) ◽

pp. 3775-3782 ◽

Cited By ~ 6

Author(s):

Lyticia A. Ochola ◽

Cyrus Ayieko ◽

Lily Kisia ◽

Ng'wena G. Magak ◽

Estela Shabani ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Severe Disease ◽

Clinical Malaria ◽

Necrosis Factor Alpha ◽

Content Type ◽

Highland Area ◽

Cytokine Responses ◽

Increased Risk ◽

Tnf Α ◽

Ifn Γ

ABSTRACTIndividuals naturally exposed toPlasmodium falciparumlose clinical immunity after a prolonged lack of exposure.P. falciparumantigen-specific cytokine responses have been associated with protection from clinical malaria, but the longevity ofP. falciparumantigen-specific cytokine responses in the absence of exposure is not well characterized. A highland area of Kenya with low and unstable malaria transmission provided an opportunity to study this question. The levels of antigen-specific cytokines and chemokines associated in previous studies with protection from clinical malaria (gamma interferon [IFN-γ], interleukin-10 [IL-10], and tumor necrosis factor alpha [TNF-α]), with increased risk of clinical malaria (IL-6), or with pathogenesis of severe disease in malaria (IL-5 and RANTES) were assessed by cytometric bead assay in April 2008, October 2008, and April 2009 in 100 children and adults. During the 1-year study period, none had an episode of clinicalP. falciparummalaria. Two patterns of cytokine responses emerged, with some variation by antigen: a decrease at 6 months (IFN-γ and IL-5) or at both 6 and 12 months (IL-10 and TNF-α) or no change over time (IL-6 and RANTES). These findings document thatP. falciparumantigen-specific cytokine responses associated in prior studies with protection from malaria (IFN-γ, TNF-α, and IL-10) decrease significantly in the absence ofP. falciparumexposure, whereas those associated with increased risk of malaria (IL-6) do not. The study findings provide a strong rationale for future studies of antigen-specific IFN-γ, TNF-α, and IL-10 responses as biomarkers of increased population-level susceptibility to malaria after prolonged lack ofP. falciparumexposure.

Download Full-text

Porphyromonas gingivalis Infection-Associated Periodontal Bone Resorption Is Dependent on Receptor Activator of NF-κB Ligand

Infection and Immunity ◽

10.1128/iai.00043-13 ◽

2013 ◽

Vol 81 (5) ◽

pp. 1502-1509 ◽

Cited By ~ 38

Author(s):

Xiaozhe Han ◽

Xiaoping Lin ◽

Xiaoqian Yu ◽

Jiang Lin ◽

Toshihisa Kawai ◽

...

Keyword(s):

B Cells ◽

Bone Resorption ◽

Fusion Protein ◽

Porphyromonas Gingivalis ◽

Nuclear Factor Κb ◽

Infected Group ◽

T And B Cells ◽

Content Type ◽

Receptor Activator ◽

Control Fusion

ABSTRACTPorphyromonas gingivalisis one of the oral microorganisms associated with human chronic periodontitis. The purpose of this study is to determine the role of the receptor activator of nuclear factor-κB ligand (RANKL) inP. gingivalisinfection-associated periodontal bone resorption. Inbred female Rowett rats were infected orally on four consecutive days (days 0 to 3) with 1 × 109P. gingivalisbacteria (strain ATCC 33277). Separate groups of rats also received an injection of anti-RANKL antibody, osteoprotegerin fusion protein (OPG-Fc), or a control fusion protein (L6-Fc) into gingival papillae in addition toP. gingivalisinfection. Robust serum IgG and salivary IgA antibody (P< 0.01) and T cell proliferation (P< 0.05) responses toP. gingivaliswere detected at day 7 and peaked at day 28 inP. gingivalis-infected rats. Both the concentration of soluble RANKL (sRANKL) in rat gingival tissues (P< 0.01) and periodontal bone resorption (P< 0.05) were significantly elevated at day 28 in theP. gingivalis-infected group compared to levels in the uninfected group. Correspondingly, RANKL-expressing T and B cells in rat gingival tissues were significantly increased at day 28 in theP. gingivalis-infected group compared to the levels in the uninfected group (P< 0.01). Injection of anti-RANKL antibody (P< 0.05) or OPG-Fc (P< 0.01), but not L6-Fc, into rat gingival papillae afterP. gingivalisinfection resulted in significantly reduced periodontal bone resorption. This study suggests thatP. gingivalisinfection-associated periodontal bone resorption is RANKL dependent and is accompanied by increased local infiltration of RANKL-expressing T and B cells.

Download Full-text

Fusobacterium nucleatum Infection of Colonic Cells Stimulates MUC2 Mucin and Tumor Necrosis Factor Alpha

Infection and Immunity ◽

10.1128/iai.05118-11 ◽

2011 ◽

Vol 79 (7) ◽

pp. 2597-2607 ◽

Cited By ~ 59

Author(s):

Poonam Dharmani ◽

Jaclyn Strauss ◽

Christian Ambrose ◽

Emma Allen-Vercoe ◽

Kris Chadee

Keyword(s):

Tumor Necrosis ◽

Bacterial Species ◽

Fusobacterium Nucleatum ◽

Mucin Secretion ◽

Necrosis Factor Alpha ◽

Content Type ◽

Tnf Α ◽

Factor Alpha ◽

Colonic Cells ◽

Necrosis Factor

ABSTRACTThe etiology of inflammatory bowel disease is not completely known, but it is influenced by the presence of normal gut microflora as well as yet-unrecognized pathogens. The anaerobic, Gram-negative bacterial speciesFusobacterium nucleatumis a common resident of the human mouth and gut and varies in its pathogenic potential. In this study, we demonstrate that highly invasiveF. nucleatumisolates derived from the inflamed guts of Crohn's disease patients evoked significantly greater MUC2 and tumor necrosis factor alpha (TNF-α) gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection. Only liveF. nucleatuminduced mucin secretion and TNF-α expression in direct contact with and/or during invasion of colonic cells. In rat colons, mucin secretion was augmented in response to a highly invasiveF. nucleatumisolate but was unaffected by treatment with a minimally invasive strain. Taken together, these studies reveal thatF. nucleatummay represent a challenging pathogen in the etiology of gut inflammatory diseases and highlight the importance of different pathotypes of candidate bacterial species in disease pathogenesis.

Download Full-text