Toll-like Receptor 2 Functions as a Pattern Recognition Receptor for Diverse Bacterial Products

Lien, Egil; Sellati, Timothy J.; Yoshimura, Atsutoshi; Flo, Trude Helen; Rawadi, Georges; Finberg, Robert W.; Carroll, J.; Espevik, Terje; Ingalls, Robin R.; Radolf, Justin D.; Golenbock, Douglas T.

doi:10.1074/jbc.274.47.33419

Cited by 847 publications

(743 citation statements)

References 59 publications

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“…The cell culture medium used included 10% FBS, a source of LPS-binding protein (34). We consistently observed, as previously reported (11,35), that cells transfected with TLR1 alone did not respond to E. coli or N. meningitidis bacteria (data not shown). However, Fig.…”

Section: Tlr1 Modifies Tlr2-dependent Responsessupporting

confidence: 91%

Evidence for an Accessory Protein Function for Toll-Like Receptor 1 in Anti-Bacterial Responses

Wyllie

Kiss-Tóth

Visintin

et al. 2000

The Journal of Immunology

245

151

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Members of the Toll-like receptor (TLR) family are components of the mammalian anti-microbial response, signaling with a domain closely related to that of IL-1 receptors. In this report the expression and function of TLR1, a TLR of unknown function, are examined. TLR1 is expressed by monocytes, as demonstrated using a novel mAb. Monocytes also express TLR2. TLR1 transfection of HeLa cells, which express neither TLR1 nor TLR2, was not sufficient to confer responsiveness to several microbial extracts. However, cotransfection of TLR1 and TLR2 resulted in enhanced signaling by HeLa cells to soluble factors released from Neisseria meningitidis relative to the response with either TLR alone. This phenomenon was also seen with high concentrations of some preparations of LPS. The N. meningitidis factors recognized by TLR1/TLR2 were not released by N. meningitidis mutant in the LpxA gene. Although LpxA is required for LPS biosynthesis, because cooperation between TLR1 and TLR2 was not seen with all LPS preparations, the microbial component(s) TLR1/2 recognizes is likely to be a complex of LPS and other molecules or a compound metabolically and chemically related to LPS. The functional IL-1R consists of a heterodimer; this report suggests a similar mechanism for TLR1 and TLR2, for certain agonists. These data further suggest that mammalian responsiveness to some bacterial products may be mediated by combinations of TLRs, suggesting a mechanism for diversifying the repertoire of Toll-mediated responses.

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Section: Tlr1 Modifies Tlr2-dependent Responsessupporting

confidence: 91%

Evidence for an Accessory Protein Function for Toll-Like Receptor 1 in Anti-Bacterial Responses

Wyllie

Kiss-Tóth

Visintin

et al. 2000

The Journal of Immunology

245

151

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“…These genes include TLR2 and LY96. TLR2 is known to be upregulated in response to peptidoglycan, lipoteichoic acid, 29 and bacterial lipoproteins 30 or LPS. TLR4 is activated by the LPS of Gram-negative bacteria 31 and LY96 is a protein associated with this receptor.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

et al. 2007

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Pathogenic mechanisms associated with Helicobacter pylori infection enhance susceptibility of the gastric epithelium to carcinogenic conversion. We have characterized the gene expression profiles of gastric biopsies from 69 French Caucasian patients, of which 43 (62%) were infected with H. pylori. The bacterium was detected in 27 of the 42 antral biopsies examined and in 16 of the 27 fundic biopsies. Infected biopsies were selected for the presence of chronic active gastritis, in absence of metaplasia and dysplasia of the gastric mucosa. Infected antral and fundic biopsies exhibited distinct transcriptional responses. Altered responses were linked with: (1) the extent of polymorphonuclear leukocyte infiltration, (2) bacterial density, and (3) the presence of the virulence factors vacA, babA2, and cagA. Robust modulation of transcripts associated with Toll-like receptors, signal transduction, the immune response, apoptosis, and the cell cycle was consistent with expected responses to Gram-negative bacterial infection. Altered expression of interferon-regulated genes (IFITM1, IRF4, STAT6), indicative of major histocompatibility complex (MHC) II-mediated and Th1-specific responses, as well as altered expression of GATA6, have previously been described in precancerous states. Upregulation of genes abundantly expressed in cancer tissues (UBD, CXCL13, LY96, MAPK8, MMP7, RANKL, CCL18) or in stem cells (IFITM1 and WFDC2) may reveal a molecular switch towards a premalignant state in infected tissues. Tissue microarray analysis of a large number of biopsies, which were either positive or negative for the cag-A virulence factor, when compared to each other and to noninfected controls, confirmed observed gene alterations at the protein level, for eight key transcripts. This study provides 'proof-of-principle' data for identifying molecular mechanisms driving H. pylori-associated carcinogenesis before morphological evidence of changes along the neoplastic progression pathway. Modern Pathology (2007) 20, 974-989;

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“…TLR2-dependent cell activation was observed in response to lipoproteins from T. pallidum and B. burgdorferi as well as LPS from Leptospira interrogans [14][15][16]. New types of glycolipids were recently extracted from small-sized Treponema species including T. denticola, T. maltophilum, and T. brennaborense [17,18].…”

Section: Introductionmentioning

confidence: 99%

Treponemal glycoconjugate inhibits Toll‐like receptor ligand‐induced cell activation by blocking LPS‐binding protein and CD14 functions

2003

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Spirochetes are well-known as causative agents of various chronic infectious diseases. Glycolipids of small-sized Treponema spirochetes have been shown to exhibit immunostimulating activities. In this study, we found that a glycoconjugate preparation obtained from Treponema medium (Tm-Gp), an intermediate-sized oral Treponema seen in subgingival plaque from patients with chronic periodontal diseases, diminished the LPS-induced activation of a human monocytic cell line, while TNF- § -induced activation was unaffected. NF-‹ B activation in Ba/F3 cells expressing murine Toll-like receptor (TLR) 4 and MD-2 was inhibited by Tm-Gp in a CD14/LPS-binding protein (LBP)-dependent manner when stimulated with LPS or its active center lipid A but not when stimulated with Taxol. Tm-Gp blocked the binding of LPS to immobilized CD14 and LBP and inhibited nitric oxide (NO) production by a murine M ¤ cell line following stimulation with peptidoglycan and LPS in the presence of FBS, while NO production in response poly (I:C) RNA or CpG DNA remained unaffected. The inhibitory effects of Tm-Gp seem to be attributable to the lipophilic portion of the glycoconjugate. These results indicate that T. medium contains a glycoconjugate possessing an inhibitory effect on TLR-mediated cell activation through interaction with LBP and CD14.

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Toll-like Receptor 2 Functions as a Pattern Recognition Receptor for Diverse Bacterial Products

Cited by 847 publications

References 59 publications

Evidence for an Accessory Protein Function for Toll-Like Receptor 1 in Anti-Bacterial Responses

Evidence for an Accessory Protein Function for Toll-Like Receptor 1 in Anti-Bacterial Responses

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

Treponemal glycoconjugate inhibits Toll‐like receptor ligand‐induced cell activation by blocking LPS‐binding protein and CD14 functions

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