Interplay of the Gastric Pathogen Helicobacter pylori with Toll-Like Receptors

Table 1

Targeted TLR receptors with proposed role during infection with H. pylori.

TLR receptor	Host cells and mouse lines used	H. pylori strain(s) used	Applied methods	Proposed role during infection	References
TLR2	AGS, HEK293, MKN45, CHO	26695, LC11, 98, 99	RT-PCR, LRGA	NF-κB activation and chemokine expression	[28]
	HEK293	26695	ELISA, IP, WB, SPIA	MAPK activation and chemokine expression	[39]
	HEK293, PBMCs, primary human monocytes and macrophages, PECs	SS1, 43504, Astra 244	ELISA, RT-PCR, cDNA-MA	Intact bacteria activate TLR-2, while LPS activates TLR-4	[29]
	mBMDCs	SS1, J99, TX30, B128	ELISA, RT-PCR, cDNA-MA, FACS, LRGA, KD	Activates TLRs to induce production of pro- and anti-inflammatory cytokines	[30]
	MKN28, MKN45, HEK293, T24, THP1	Clinical strains	ELISA, FACS, RT-PCR, LRGA, WB	Highly purified LPS is a weak agonist, activates NF-κB through TLR-2/1 heterodimer	[35]
	KATO III	43504	ELISA, ABB, RT-PCR, NB, WB, TFA, ICC, RPT	HpHSP60 is a ligand, activates NF-κB and chemokine expression in epithelial cells	[36]
	NOMO1, U937	43504	ELISA, ABB, TFA, RT-PCR, siRNA, SPIA, FACS, WB, RPT	HpHSP60 is a ligand, activates MAPK and chemokine expression in monocytes	[37]
	PBMCs, primary human monocytes, neutrophils and T-cells	n.p.	ELISA, RT-PCR, ELISPOT, NF-κBRA, FACS, TCA, CRA, RPT	HpNAP activates proinflammatory cytokine expression and T-cell responses	[38]
	AGS, MKN45	Clinical strains	EMSA, RT-PCR, WB, IFM, LGRA, IP, KA	NF-κB activation and COX-2 overexpression	[40]
	AGS, MKN45, HUVEC	Clinical strains	ELISA, DAPA, EMSA, WB, ChIP, RT-PCR, LGRA, MGTA	COX-2 induction and increased cell invasion and angiogenesis	[41]
TLR4	AGS, HEK293, MKN45, CHO	26695, LC11, 98, 99	RT-PCR, LRGA	NF-κB activation and chemokine expression	[28]
	HEK293, PBMCs, primary human monocytes and macrophages, PECs	SS1, 43504, Astra 244	ELISA, RT-PCR, cDNA-MA	Intact bacteria activate TLR-2, while LPS activates TLR-4	[29]
	AGS, MKN-7, MKN-28, MKN-45, THP-1	43504, TN583, clinical strains	LCM, IHC, RT-PCR, FACS, LGRA	NF-κB activation and chemokine expression	[42]
	MKN45, TMK1, J774A.1, THP1, PECs	TN2	ELISA, ABB, TLR-SA, RT-PCR, EMSA, RPA, IP, WB, cDNA-MA	NF-κB activation is cagPAI-dependent in epithelial cells, but cagPAI-independent in monocytes/macrophages	[43]
	AGS, MKN45, CHO, T84, THP1	LC11, LC20	ELISA, RT-PCR, WB, FACS, IFM, SEM	Upregulation of TLR expression and chemokine secretion	[44]
	Gastric mucosal cells	11637, 11638, clinical strains	RT-PCR, SB, WB, NB	Upregulation of superoxides in gastric pit cells	[45]
	HEK293; C57BL/6J mice in vivo	J99, B128, X47	FBA, MS, PA, TLR-SA, MCA, NF-κBRA, FM	Dephosphorylation of lipid-A reduces recognition and increases colonization	[46]
	AGS, gastric biopsies	J99, clinical strains	RT-PCR	TLR expression is not affected in gastric biopsies of infected patients	[47]
	Gastric biopsies	Clinical strains	ICH, IFM, CSLM	Shifting of subcellular localization of TLRs	[48]
TLR5	AGS, HEK293, MKN45, CHO	26695, LC11, 98, 99	RT-PCR, LRGA	NF-κB activation and chemokine expression	[28]
	HEK293	26695	ELISA, IP, WB, SPIA	MAPK activation and chemokine expression	[39]
	AGS, T84, MDCK	49503	ELISA, WB, RPT,	Flagellin evades TLR5 recognition	[49]
	CHO K1	G27, clinical strains	LRGA, WB, RPT, BIT, MA	Flagellin evades TLR5 recognition	[50]
	HEK293; BALB/c mice in vivo	SS1S	ELISA, CD, LRGA, RT-PCR, WB, RPT	Chimeric flagellin can activate immune responses	[51]
	HEK293, THP1	P1, P12, P310, 26695	ASPAB, ELISA, IFM, RT-PCR, TLR-SA, LRGA, WB	cagPAI status can change TLR activated production of cytokine/chemokine	[34]
	GES1	26695	cDNA-MA, FACS, RT-PCR, SEM	Spiral and coccoid forms can influence TLR expression	[52]
	AGS, gastric biopsies	J99, clinical strains	RT-PCR	TLR expression is not affected in gastric biopsies of infected patients	[47]
	Gastric biopsies	Clinical strains	ICH, IFM, CSLM	Shifting of subcellular localization of TLRs	[48]
	Gastric biopsies	Clinical strains	ICH, IFM, CSLM	Shifting of subcellular localization of TLRs	[53]
TLR8	PBMCs, primary human monocytes, HeLa, HEK293, HEK293T, HEK293FT, THP1	251, B128	ELISA, RT-PCR, LGRA, CSLM, BIT, FACS	Bacterial phagocytosis increases TLRs activation and cytokine secretion	[54]
TLR9	mBMDCs	SS1, J99, TX30, B128	ELISA, RT-PCR, cDNA-MA, FACS, LRGA, KD	Activates TLRs to induce production of proinflammatory cytokines	[30]
	AGS, MKN45, HUVEC	Clinical strains	ELISA, DAPA, EMSA, WB, ChIP, RT-PCR, LGRA, MGTA	COX-2 induction and increased cell invasion and angiogenesis	[41]
	AGS, MKN45	Clinical strains	EMSA, RT-PCR, WB, IFM, LGRA, IP, KA	NF-κB activation and COX-2 overexpression	[40]
	Gastric biopsies	Clinical strains	ICH, IFM, CSLM	Shifting of subcellular localization of TLRs	[48, 53]
	Primary human neutrophils	26695, G27, 8822, clinical strains	ELISA, FACS	cagPAI dependent production of pro- and anti-inflammatory cytokines	[55]
	Gastric tissue, C57BL/6J mice	SS1	IHC, RT-PCR, MPA, CSLM	Type-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.