Table 1: Targeted TLR receptors with proposed role during infection with H. pylori.

TLR receptorHost cells and mouse lines usedH. pylori strain(s) usedApplied methodsProposed role during infection References

TLR2AGS, HEK293, MKN45, CHO26695, LC11, 98, 99RT-PCR, LRGANF-κB activation and chemokine expression[28]
HEK29326695ELISA, IP, WB, SPIAMAPK activation and chemokine expression[39]
HEK293, PBMCs, primary human monocytes and macrophages, PECsSS1, 43504, Astra 244ELISA, RT-PCR, cDNA-MAIntact bacteria activate TLR-2, while LPS activates TLR-4[29]
mBMDCsSS1, J99, TX30, B128ELISA, RT-PCR, cDNA-MA, FACS, LRGA, KDActivates TLRs to induce production of pro- and anti-inflammatory cytokines[30]
MKN28, MKN45, HEK293, T24, THP1Clinical strainsELISA, FACS, RT-PCR, LRGA, WBHighly purified LPS is a weak agonist, activates NF-κB through TLR-2/1 heterodimer[35]
KATO III43504ELISA, ABB, RT-PCR, NB, WB, TFA, ICC, RPTHpHSP60 is a ligand, activates NF-κB and chemokine expression in epithelial cells[36]
NOMO1, U93743504ELISA, ABB, TFA, RT-PCR, siRNA, SPIA, FACS, WB, RPTHpHSP60 is a ligand, activates MAPK and chemokine expression in monocytes[37]
PBMCs, primary human monocytes, neutrophils and T-cellsn.p.ELISA, RT-PCR, ELISPOT, NF-κBRA, FACS, TCA, CRA, RPTHpNAP activates proinflammatory cytokine expression and T-cell responses[38]
AGS, MKN45Clinical strainsEMSA, RT-PCR, WB, IFM, LGRA, IP, KANF-κB activation and COX-2 overexpression[40]
AGS, MKN45, HUVECClinical strainsELISA, DAPA, EMSA, WB, ChIP, RT-PCR, LGRA, MGTACOX-2 induction and increased cell invasion and angiogenesis[41]

TLR4AGS, HEK293, MKN45, CHO26695, LC11, 98, 99RT-PCR, LRGANF-κB activation and chemokine expression[28]
HEK293, PBMCs, primary human monocytes and macrophages, PECsSS1, 43504, Astra 244ELISA, RT-PCR, cDNA-MAIntact bacteria activate TLR-2, while LPS activates TLR-4[29]
AGS, MKN-7, MKN-28, MKN-45, THP-143504, TN583, clinical strainsLCM, IHC, RT-PCR, FACS, LGRANF-κB activation and chemokine expression[42]
MKN45, TMK1, J774A.1, THP1, PECsTN2ELISA, ABB, TLR-SA, RT-PCR, EMSA, RPA, IP, WB, cDNA-MANF-κB activation is cagPAI-dependent in epithelial cells, but cagPAI-independent in monocytes/macrophages[43]
AGS, MKN45, CHO, T84, THP1LC11, LC20ELISA, RT-PCR, WB, FACS, IFM, SEMUpregulation of TLR expression and chemokine secretion[44]
Gastric mucosal cells11637, 11638, clinical strainsRT-PCR, SB, WB, NBUpregulation of superoxides in gastric pit cells[45]
HEK293
C57BL/6J mice in vivo
J99, B128, X47FBA, MS, PA, TLR-SA, MCA, NF-κBRA, FMDephosphorylation of lipid-A reduces recognition and increases colonization[46]
AGS, gastric biopsiesJ99, clinical strainsRT-PCRTLR expression is not affected in gastric biopsies of infected patients[47]
Gastric biopsiesClinical strainsICH, IFM, CSLMShifting of subcellular localization of TLRs [48]

TLR5AGS, HEK293, MKN45, CHO26695, LC11, 98, 99RT-PCR, LRGANF-κB activation and chemokine expression[28]
HEK29326695ELISA, IP, WB, SPIAMAPK activation and chemokine expression[39]
AGS, T84, MDCK49503ELISA, WB, RPT, Flagellin evades TLR5 recognition[49]
CHO K1G27, clinical strainsLRGA, WB, RPT, BIT, MAFlagellin evades TLR5 recognition[50]
HEK293
BALB/c mice in vivo
SS1SELISA, CD, LRGA, RT-PCR, WB, RPTChimeric flagellin can activate immune responses[51]
HEK293, THP1P1, P12, P310, 26695ASPAB, ELISA, IFM, RT-PCR, TLR-SA, LRGA, WBcagPAI status can change TLR activated production of cytokine/chemokine [34]
GES126695cDNA-MA, FACS, RT-PCR, SEM Spiral and coccoid forms can influence TLR expression[52]
AGS, gastric biopsiesJ99, clinical strainsRT-PCRTLR expression is not affected in gastric biopsies of infected patients[47]
Gastric biopsiesClinical strainsICH, IFM, CSLMShifting of subcellular localization of TLRs [48]
Gastric biopsiesClinical strainsICH, IFM, CSLMShifting of subcellular localization of TLRs[53]

TLR8PBMCs, primary human monocytes, HeLa, HEK293, HEK293T, HEK293FT, THP1251, B128ELISA, RT-PCR, LGRA, CSLM, BIT, FACSBacterial phagocytosis increases TLRs activation and cytokine secretion[54]

TLR9mBMDCsSS1, J99, TX30, B128ELISA, RT-PCR, cDNA-MA, FACS, LRGA, KDActivates TLRs to induce production of proinflammatory cytokines[30]
AGS, MKN45, HUVECClinical strainsELISA, DAPA, EMSA, WB, ChIP, RT-PCR, LGRA, MGTACOX-2 induction and increased cell invasion and angiogenesis[41]
AGS, MKN45Clinical strainsEMSA, RT-PCR, WB, IFM, LGRA, IP, KANF-κB activation and COX-2 overexpression[40]
Gastric biopsiesClinical strainsICH, IFM, CSLMShifting of subcellular localization of TLRs [48, 53]
Primary human neutrophils26695, G27, 8822, clinical strainsELISA, FACScagPAI dependent production of pro- and anti-inflammatory cytokines[55]
Gastric tissue, C57BL/6J miceSS1IHC, RT-PCR, MPA, CSLMType-I interferon mediated anti-inflammatory response at early phase infection[56]

AB: antibody; ABB: antibody blocking; ASPAB: activation specific phospho antibodies; BIT: bioinformatic tools; cagPAI: cytotoxin-associated genes pathogenicity island; CD: circular dichroism; cDNA-MA: cDNA micro/macroarray; ChIP: chromatin immunoprecipitation; COX-2: cyclooxygenase-2; CRA: chromium release assay; CSLM: confocal laser scanning microscopy; DAPA: DNA affinity protein binding assay; ELISA: enzyme-linked immunosorbent assay; ELISPOT: enzyme-linked immunospot; EMSA: electrophoretic mobility shift assay; FACS: fluorescence-activated cell sorting; FBA: fluorescent binding assay; FM: fluorescence microscopy; HPA: histopathological analysis; HSP: heat shock protein; IFM: immunofluorescence microscopy; ICC: immunocytochemistry; IHC: immunohistochemistry; IP: immunoprecipitation; KA: kinase assay; KD: knockdown of genes; LCM: laser capture microdissection; LRGA: luciferase reporter gene assay; MAPK: mitogen-activated protein kinases; MA: motility assay; mBMDCs: mouse bone marrow derived DCs; MCA: mouse colonization assay; MGTA: matrigel tube formation assay; MPA: myeloperoxidase activity assay; MS: mass spectrometry; NAP: neutrophil activating protein; NB: northern blotting; NF-κB: nuclear factor kappa B; NF-κBRA: nuclear factor kappa B reporter assay; n.p.: not provided; PA: phosphatase assay; PBMCs: peripheral blood mononuclear cells; PECs: peritoneal exudate cells; RPA: RNAse protection assay; RPT: recombinant protein techniques; RT-PCR: real-time/reverse transcriptase PCR; SB: southern blotting; SEM: scanning electron microscopy; siRNA: small interfering RNA; SPIA: signaling pathway inhibitor assay; TCA: T-cell clonal assays; TFA: transcription factor assay; TLR: Toll-like receptor; TLR-SA: TLR signaling assay; WB: western blotting.