Toll-Like Receptor 2-Mediated Interleukin-8 Expression in Gingival Epithelial Cells by the
            <i>Tannerella forsythia</i>
            Leucine-Rich Repeat Protein BspA

Onishi, Shinsuke; Honma, Kiyonobu; Liang, Shuang; Stathopoulou, Panagiota G.; Kinane, Denis F.; Hajishengallis, George; Sharma, Ashu

doi:10.1128/iai.01139-07

Cited by 63 publications

(68 citation statements)

References 35 publications

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“…Thus, they appear to be ideal ligands for a pattern recognition receptor. Interestingly, BspA interacts also with other pattern recognition receptors, such as the Toll-like receptor TLR2 (41), and recent findings suggest that Lrr domains are needed for this interaction (42). Thus, it may be that Lrr domains can serve as recognition motifs for other pattern recognition receptors as well.…”

Section: Discussionmentioning

confidence: 99%

Leucine-rich Repeats of Bacterial Surface Proteins Serve as Common Pattern Recognition Motifs of Human Scavenger Receptor gp340

Loimaranta¹,

Hytönen

Pulliainen

et al. 2009

Journal of Biological Chemistry

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Scavenger receptors are innate immune molecules recognizing and inducing the clearance of non-host as well as modified host molecules. To recognize a wide pattern of invading microbes, many scavenger receptors bind to common pathogenassociated molecular patterns, such as lipopolysaccharides and lipoteichoic acids. Similarly, the gp340/DMBT1 protein, a member of the human scavenger receptor cysteine-rich protein family, displays a wide ligand repertoire. The peptide motif VEVLXXXXW derived from its scavenger receptor cysteine-rich domains is involved in some of these interactions, but most of the recognition mechanisms are unknown. In this study, we used mass spectrometry sequencing, gene inactivation, and recombinant proteins to identify Streptococcus pyogenes protein Human gp340, also known as DMBT1 (deleted in malignant brain tumors 1), belongs to the innate immune protein family of scavenger receptor cysteine-rich (SRCR) 2 proteins, all of which contain one or more evolutionarily conserved SRCR domain linked to other conserved protein domains (1, 2). Many of these proteins serve as pattern recognition receptors for innate immunity. gp340 is expressed by epithelial cells and cells of the immune system, and its expression is up-regulated after inflammatory stimuli (3, 4). It inhibits bacterial invasion to epithelial cells and the secretion of proinflammatory cytokines (5-7).Thus, it appears to be an important mediator of host immune responses to various microbes and was recently linked to Crohn disease, a human inflammatory bowel disease (8). gp340 is also found in human secretions like tears and saliva, and the salivary form has long been known as salivary agglutinin, which is an important molecule in oral biofilm formation and is suggested to have a role in dental caries development (9 -12). The mechanisms of gp340 action in these different biological contexts are not known. Common to all scavenger receptors, the ligand repertoire of gp340 is wide; it binds many different types of bacteria as well as viruses (10,13,14). The wide ligand recognition pattern of scavenger receptors is thought to be based on the recognition of common microbial structures, such as lipopolysaccharides and lipoteichoic acids, but in the case of gp340, specific bacterial surface proteins are reported to be involved in the interactions characterized (15-18). Because the importance of gp340/salivary agglutinin in the oral environment has been evident for a long time, most of our knowledge of gp340-microbial interactions is from studies with oral bacteria. For example, viridans streptococci, such as Streptococcus mutans and Streptococcus gordonii, interact with saliva gp340 via their surface proteins AgI/II and the sialic acid-binding Hsa or GspB adhesin. In these interactions, gp340 shows a peculiar fluid phase versus surfaceadsorbed behavior, as evidenced by AgI/II polypeptides primarily mediating aggregation of bacteria by fluid phase gp340, whereas the Hsa adhesin primarily mediates adhesion of S. gordonii to surface-bound gp340 (18)...

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Section: Discussionmentioning

confidence: 99%

Leucine-rich Repeats of Bacterial Surface Proteins Serve as Common Pattern Recognition Motifs of Human Scavenger Receptor gp340

Loimaranta¹,

Hytönen

Pulliainen

et al. 2009

Journal of Biological Chemistry

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“…This family, originally identified in Treponema pallidum, is comprised of proteins that are located on the cell surface (26,27). Furthermore, LRR TP proteins were shown previously to play a role in surface adherence and aggregation (26,37,38). AdpC contains six typical LRR motifs in which most of the leucine-like residues are conserved compared to the BspA protein of T. forsythia (37,42).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, LRR TP proteins were shown previously to play a role in surface adherence and aggregation (26,37,38). AdpC contains six typical LRR motifs in which most of the leucine-like residues are conserved compared to the BspA protein of T. forsythia (37,42).…”

Section: Discussionmentioning

confidence: 99%

AdpC Is aPrevotella intermedia17 Leucine-Rich Repeat Internalin-Like Protein

et al. 2010

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The oral bacterium Prevotella intermedia attaches to and invades gingival epithelial cells, fibroblasts, and endothelial cells. Several genes encoding proteins that mediate both the adhesion and invasion processes are carried on the genome of this bacterium. Here, we characterized one such protein, AdpC, belonging to the leucine-rich repeat (LRR) protein family. Bioinformatics analysis revealed that this protein shares similarity with the Treponema pallidum LRR (LRR TP ) family of proteins and contains six LRRs. Despite the absence of a signal peptide, this protein is localized on the bacterial outer membrane, indicating that it is transported through an atypical secretion mechanism. The recombinant form of this protein (rAdpC) was shown to bind fibrinogen. In addition, the heterologous host strain Escherichia coli BL21 expressing rAdpC (V2846) invaded fibroblast NIH 3T3 cells at a 40-foldhigher frequency than control E. coli BL21 cells expressing a sham P. intermedia 17 protein. Although similar results were obtained by using human umbilical vein endothelial cells (HUVECs), only a 3-fold-increased invasion of V2846 into oral epithelial HN4 cells was observed. Thus, AdpC-mediated invasion is cell specific. This work demonstrated that AdpC is an important invasin protein of P. intermedia 17.

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“…Although the identity of these components is currently unknown, an earlier study has demonstrated that T. forsythia S-layer proteins also mediate attachment to and invasion of KB epithelial cells (Sabet et al, 2003). Interestingly, T. forsythia whole cells and their components have been shown to activate the pattern recognition receptor Toll-like receptor (TLR)2 (Hasebe et al, 2004;Kikkert et al, 2007;Onishi et al, 2008), and PI3K is also a downstream target of TLR2 activation. Thus, the contribution of BspA in invasion and host cell signalling in the context of the bacterial whole cell could not be discerned in this study.…”

Section: Tyrosine Kinase(s) and Pi3k Are Involved In T Forsythia Invmentioning

confidence: 99%

Tannerella forsythia invasion in oral epithelial cells requires phosphoinositide 3-kinase activation and clathrin-mediated endocytosis

Mishima

Sharma

2011

Microbiology

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Tannerella forsythia, a Gram-negative anaerobe implicated in periodontitis, has been detected within human buccal epithelial cells and shown to invade oral epithelial cells in vitro. We have previously shown that this bacterium triggers host tyrosine kinase-dependent phosphorylation and actin-dependent cytoskeleton reorganization for invasion. On the bacterial side, the leucine-rich repeat cell-surface BspA protein is important for entry. The present study was undertaken to identify host signalling molecules during T. forsythia entry into human oral and cervical epithelial cells. Specifically, the roles of phosphatidylinositol 3-kinase (PI3K), Rho-family GTPases, cholesterol-rich membrane microdomains and the endocytic protein clathrin were investigated. For this purpose, cell lines were pretreated with chemical inhibitors or small interfering RNAs (siRNAs) that target PI3Ks, Rho GTPases, clathrin and cholesterol (a critical component of ‘lipid rafts’), and the resulting effects on T. forsythia uptake were determined. Our studies revealed that T. forsythia entry is dependent on host PI3K signalling, and that purified BspA protein causes activation of this lipid kinase. Bacterial entry also requires the cooperation of host Rac1 GTPase. Finally, our findings indicate an important role for clathrin and cholesterol-rich lipid microdomains in the internalization process

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Toll-Like Receptor 2-Mediated Interleukin-8 Expression in Gingival Epithelial Cells by the Tannerella forsythia Leucine-Rich Repeat Protein BspA

Cited by 63 publications

References 35 publications

Leucine-rich Repeats of Bacterial Surface Proteins Serve as Common Pattern Recognition Motifs of Human Scavenger Receptor gp340

Leucine-rich Repeats of Bacterial Surface Proteins Serve as Common Pattern Recognition Motifs of Human Scavenger Receptor gp340

AdpC Is aPrevotella intermedia17 Leucine-Rich Repeat Internalin-Like Protein

Tannerella forsythia invasion in oral epithelial cells requires phosphoinositide 3-kinase activation and clathrin-mediated endocytosis

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