Toll‐like receptor 9 mediates oral bacteria‐induced IL‐8 expression in gingival epithelial cells

Kim, Young-Sook; Jo, Ah-ram; Jang, Da Hyun; Cho, Yong‐Joon; Chun, Jongsik; Min, Byung‐Moo; Choi, Youngnim

doi:10.1038/icb.2011.85

Cited by 31 publications

(40 citation statements)

References 36 publications

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“…It triggers type-I IFN production upon the detection of unmethylated CpG motifs within the DNA sequence of invading microorganisms [47]. Given that at least two cell subsets (plasmacytoid dendritic cells (pDC) and B cells) within PBMCs possess a functional TLR-9 pathway [16], we determined whether a pre-treatment with the TLR-9 inhibitor ODN TTAGGG (iODN) [48], [49] prevents the MVMp- or H-1PV-triggered IFN production in the immune cell mixture. As shown in Figure 10, we indeed observed a partial inhibition of the parvovirus-triggered productions of IFN-α (Figure 10A) and IFN-β (Figure 10B) upon treatment of the cells with the iODN, an effect not achieved at the same concentration by a control oligodeoxynucleotide (ODN TTAGGG Control) (Figure S4).…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, since the TLR-9 inhibitor ODN TTAGGG [48], [49] fully blocks the TLR-9-mediated activation of NFκB in HEK293-hTLR9 +/+ cells, but only partially inhibits the parvovirus-triggered IFN production in hPBMCs, it suggests that another factor (PRR) might contribute, besides TLR-9, to the latter cytokine synthesis. This potential additional sensor belongs most likely to the family of DNA sensors [67], [68] since both MVMp and H-1PV infections remained defective over the period of time tested, in agreement with previous data reported by our group [30] but in contradiction with others that noticed some H-1PV NS1 polypeptide expression in infected PBMCs [69].…”

Section: Discussionmentioning

confidence: 99%

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TLR-9 Contributes to the Antiviral Innate Immune Sensing of Rodent Parvoviruses MVMp and H-1PV by Normal Human Immune Cells

et al. 2013

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The oncotropism of Minute Virus of Mice (MVMp) is partially related to the stimulation of an antiviral response mediated by type-I interferons (IFNs) in normal but not in transformed mouse cells. The present work was undertaken to assess whether the oncotropism displayed against human cells by MVMp and its rat homolog H-1PV also depends on antiviral mechanisms and to identify the pattern recognition receptor (PRR) involved. Despite their low proliferation rate which represents a drawback for parvovirus multiplication, we used human peripheral blood mononuclear cells (hPBMCs) as normal model specifically because all known PRRs are functional in this mixed cell population and moreover because some of its subsets are among the main IFN producers upon infections in mammals. Human transformed models consisted in lines and tumor cells more or less permissive to both parvoviruses. Our results show that irrespective of their permissiveness, transformed cells do not produce IFNs nor develop an antiviral response upon parvovirus infection. However, MVMp- or H-1PV-infected hPBMCs trigger such defense mechanisms despite an absence of parvovirus replication and protein expression, pointing to the viral genome as the activating element. Substantial reduction of an inhibitory oligodeoxynucleotide (iODN) of the latter IFN production identified TLR-9 as a potential PRR for parvoviruses in hPBMCs. However, neither the iODN treatment nor an antibody-induced neutralization of the IFN-triggered effects restored parvovirus multiplication in these cells as expected by their weak proliferation in culture. Finally, given that a TLR-9 activation could also not be observed in parvovirus-infected human lines reported to be endowed with a functional TLR-9 pathway (Namalwa, Raji, and HEK293-TLR9+/+), our data suggest that transformed human cells do not sense MVMp or H-1PV either because of an absence of PRR expression or an intrinsic, or virus-driven defect in the endosomal sensing of the parvovirus genomes by TLR-9.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

TLR-9 Contributes to the Antiviral Innate Immune Sensing of Rodent Parvoviruses MVMp and H-1PV by Normal Human Immune Cells

et al. 2013

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“…Infection of gingival epithelial cells by F. nucleatum increases the expression of antimicrobial peptides and cytokines, such as human beta defensin (HBD)-2, HBD-3, interleukin (IL)-6, and IL-8 [22,24,32,33]. In particular, the induction of HBD-2, HBD-3, and IL-8 production by F. nucleatum depends on bacterial invasion and endosomal maturation [24,34]. After invasion, endosomes containing F. nucleatum rapidly fuse with lysosomes, and intracellular F. nucleatum is cleared via endolysosomal degradation [24].…”

Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis suppresses invasion of Fusobacterium nucleatum into gingival epithelial cells

Jung

Jun

Choi

2017

Journal of Oral Microbiology

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Invasion of periodontal pathogens into periodontal tissues is an important step that can cause tissue destruction in periodontal diseases. Porphyromonas gingivalis is a keystone pathogen and its gingipains are key virulence factors. Fusobacterium nucleatum is a bridge organism that mediates coadhesion of disease-causing late colonizers such as P. gingivalis and early colonizers during the development of dental biofilms. The aim of this study was to investigate how P. gingivalis, in particular its gingipains, influences the invasion of coinfecting F. nucleatum into gingival epithelial cells. When invasion of F. nucleatum was analyzed after 4 h of infection, invasion of F. nucleatum was suppressed in the presence of P. gingivalis compared with during monoinfection. However, coinfection with a gingipain-null mutant of P. gingivalis did not affect invasion of F. nucleatum. Inhibition of PI3K reduced invasion of F. nucleatum. P. gingivalis inactivated the PI3K/AKT pathway, which was also dependent on gingipains. Survival of intracellular F. nucleatum was promoted by P. gingivalis with Arg gingipain mutation. The results suggest that P. gingivalis, in particular its gingipains, can affect the invasion of coinfecting F. nucleatum through modulating intracellular signaling of the host cells.

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“…Secretion of IL-8 in response to TLR9, TLR2 and TLR5 stimulation and, to a lesser extent, to TLR4 stimulation has been shown in gingival epithelial cells, which is enhanced by a prior cell exposure to IFN-γ (77, 79, 149). Besides IL-8, secretion of other inflammatory cytokines directly involved in innate immunity, such as IL-1β and TNF-α, as well as that of APCs chemo-attractants has been shown.…”

Section: Tlr Expression and Responses In Human Mucosal Epithelial Tismentioning

confidence: 99%

TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens

2014

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Toll-like receptor (TLR) signaling represents one of the best studied pathways to implement defense mechanisms against invading microbes in human being as well as in animals. TLRs respond to specific microbial ligands and to danger signals produced by the host during infection, and initiate downstream cascades that activate both innate and adaptive immunity. TLRs are expressed by professional immune cells and by the large majority of non-hematopoietic cells, including epithelial cells. In epithelial tissues, TLR functions are particularly important because these sites are constantly exposed to microorganisms, due to their location at the host interface with the environment. While at these sites specific defense mechanisms and inflammatory responses are initiated via TLR signaling against pathogens, suppression or lack of TLR activation is also observed in response to the commensal microbiota. The mechanisms by which TLR signaling is regulated in mucosal epithelial cells include differential expression and levels of TLRs (and their signaling partners), their cellular localization and positioning within the tissue in a fashion that favors responses to pathogens while dampening responses to commensals and maintaining tissue homeostasis in physiologic conditions. In this review, the expression and activation of TLRs in mucosal epithelial cells of several sites of the human body are examined. Specifically, the oral cavity, the ear canal and eye, the airways, the gut, and the reproductive tract are discussed, along with how site-specific host defense mechanisms are implemented via TLR signaling.

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Toll‐like receptor 9 mediates oral bacteria‐induced IL‐8 expression in gingival epithelial cells

Cited by 31 publications

References 36 publications

TLR-9 Contributes to the Antiviral Innate Immune Sensing of Rodent Parvoviruses MVMp and H-1PV by Normal Human Immune Cells

TLR-9 Contributes to the Antiviral Innate Immune Sensing of Rodent Parvoviruses MVMp and H-1PV by Normal Human Immune Cells

Porphyromonas gingivalis suppresses invasion of Fusobacterium nucleatum into gingival epithelial cells

TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens

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