Table 1. Targeted host cell protein receptors interacting with known ligands of H. pylori.
| Host protein receptor | Bacterial factor | Host cells used | H. pylori strains used | Applied methods | Proposed role during infection and pathogenesis | References |
|---|---|---|---|---|---|---|
| β1 integrin | CagL | AGS, GD25 vs. GD25β1, knockout MEFs | P1, P12 | BBS, PCA, CAA, CD, ABB, CSLM, FESEM, RPT, PIS, siRNA, shRNA ASPAB, WB | Host cell docking of T4SS | 52 |
| AGS | 7.13, P12 | LRGA, siRNA, ELISA, WB, IP, RPT, RT-PCR, PCA | Inhibition of H,Kα -mediated gastric acid secretion | 67,68 | ||
| AGS, MKN45, HeLa, knockout MEFs | P12, purified proteins in vitro | RPT, CAA, CSA, IFM, LCI, FESEM, ASPAB, PIS, WB, PC | Cell attachment, signaling and spreading | 55,56 | ||
| AGS, WM-115 | P12 | RPT, CAA, PCA, CD, ASPAB, PAH, WB | Host cell docking of T4SS | 57 | ||
| CagA, CagI, CagY | GE11 vs. GE11β1, CHO vs. CHOβ1, HL60 vs. dHL60, AGS | P12, P145, P217 | Y2H, RPT, BBS, ABB, PDA, FACS, FESEM, PIS, WB, PC | Host cell docking of T4SS | 59,60 | |
| CagY | AGS, MKN45, HeLa, knockout MEFs | Purified proteins in vitro |
RPT, CAA, CSA | Cell attachment, signaling and spreading | 56 | |
| β3 integrin | CagL | WM-115 | Purified proteins in vitro |
CAA, PCA, NMR | Host cell docking of T4SS | 92 |
| β5 integrin | CagL | AGS, AMO, AM4, Mongolian gerbils | P1, P12, B8, 7.13, 26695, J99, Tx30a, Ka125, 1061 | BBS, RT-PCR, LRGA, siRNA, PIS, WB, IHC | Host cell docking of T4SS, gastrin expression | 91 |
| CD18 (β2 integrin) | VacA | Primary T cells, Jurkat T cells, PBMCs, SKW3 T cells, SK-b2.7 (β2-minus), EL4 T cells | P12, 60190 | FACS, CLSM, IFM, LCI, ELISA, TCPA, WB | Receptor for VacA, deregulation of NFAT and T-cell proliferation | 104 |
| CD46 | Urease A, AhpC | AGS, Kato-III | J99, 26695, HPAG1, 67:21 | RPT, FACS, IFM, CAA, PCA, ELISA, MS | CD46 inhibits urease and is bactericidal to H. pylori | 42 |
| CD74 | Urease B | N87, Kato-III, HS738, P3HR1-B | LC11, 26695, 43504, 51B | FACS, IP, CAA, WB | NFκB activation, changed antigen presentation by MHCII | 39,40 |
| c-Met | T4SS, CagA | AGS, HeLa | P1 | ASPAB, IFM, IP, WB, siRNA, PIS, CMA | Epithelial cell motility | 79 |
| T4SS, CagA | AGS | 26695, 60190 | PIS, CMIA, siRNA, IHC, CSLM, IP, CZG, WB | Epithelial cell invasion | 80,81 | |
| CagA | AGS, EAGS, 293T, BING, Kato-III, CIH28, Mongolian gerbils | 11637, 43504, 43579, 26695, B128 | IP, PDA, siRNA, CSLM, IHC, LRGA, RT-PCR, ELISA, WB | Epithelial cell proliferation and inflammation | 82 | |
| E-cadherin | HtrA | MKN28 | P12 | CSLM, CZG, ICA, TWA, PIS, WB | Epithelial barrier disruption | 12 |
| CagA | MKN28, MKN45 | No infections, CagA transfection | CSLM, IP, LRGA, cDNA-MA, WB | β-catenin activation | 101 | |
| EGF receptor (ErbB1) | VacA | HeLa | 43504 | ABB, IP, PIS, WB | Internalization of VacA by endocytosis | 151 |
| T4SS | AGS | 60190, J44, 43504, J166, J238, J68, 107A | LRGA, PIS, ASPAB, RGAA, ELISA, RT-PCR, EMSA, WB | IL-8 secretion, EGR1 activation | 72,75 | |
| T4SS | AGS, ImPC, kinase-defective EGFR mice | 7.13 | ABB, TUNEL, FACS, ASPAB, PIS, IHC, IFM, WB | Anti-apoptotic signaling | 76 | |
| CagL | AGS, HeLa, MKN28, knockout MEFs | 7.13, P12 | IP, RPT, CAA, CSA, IFM, LCI, ASPAB, PIS, LRGA, siRNA, ELISA, RT-PCR, PCA, WB | Activation of NFκB, cell attachment, signaling and spreading | 56,68 | |
| ErbB2 (Her2-NEU) | T4SS | AGS, HeLa | P1 | ASPAB, WB, PIS, CMA | unknown | 79 |
| T4SS, VacA | AGS | P1, P12, 60190, P310, 26695, P277, 11637 | CMA, IFM, ASPAB, siRNA, WB | Cell signaling and motility, VacA exhibits counteracting activities | 78 | |
| ErbB3 | CagL | AGS, MKN45, HeLa, knockout MEFs | Purified proteins in vitro |
RPT, CAA, CSA, IFM, FESEM, ASPAB, WB | Cell attachment, signaling and spreading | 56 |
| Fibronectin | VacA | HeLa, AGS | 49503 | CAA, IFM, PIS | Cell signaling | 31 |
| HtrA | MKN28 | P12 | CSLM, CZG, ICA, TWA, PIS, WB | Epithelial barrier disruption | 12 | |
| GP130 | CagA | AGS | 60190, 147C, 147A | CMA, CSLM, ASPAB, IP, PIS, RT-PCR, EMSA, WB | Phosphorylated CagA affects SHP2/ERK and JAK/STAT signaling | 90 |
| ICAM1 and LFA1 | T4SS | U937, JoskM | P1, P12, G27 | FACS, IFM, ABB, WB | Homotypic aggregation of APCs, CD4+ T cell deregulation | 127 |
| Laminin | AlpA/B | AGS, Mongolian Gerbils | 26695, SS1 | FACS, BBS, CAA, IHC | Enhanced binding and inflammation | 25 |
| MHC II | Urease B | Kato-III, N87, COS-1, B cell lines |
Purified proteins in vitro |
FACS, ELISA, bead assays, capture assays, CAA | Altered antigen presentation through MHC II | 121 |
| NOD1 | Peptido-glycan | AGS, AGS NOD1KD cells, HEK293, NOD1−/− mice, primary cells | 251, 26695, 189, 249 | LRGA, siRNA, PGN labeling, HPLC, IFM, IHC, GPA,ELISA, RT-PCR, PIS, WB | Activation of NFκB (pro- inflammatory responses) | 9,152 |
| Peptido-glycan-peptide | AGS, HT29, NOD1−/− knockout mice, primary cells, knockout MEFs | TN2-GF4 | ASPAB, LRGA, ELISA, siRNA, IP, PIS, WB | Interferon γ and ISGF3 induction | 51 | |
| NOD2 | T4SS | BMDCs from NOD2−/− and other knockout mice | 26695, P1, P12, G27, SPM326 | ELISA, GPA, RT-PCR, WB | Activation of inflammasome | 150 |
| RPTP-α | VacA | G401, Cos-7, AZ-251 | Purified VacA | IP, CAA, FACS, MS, PCA, WB | VacA receptor | 30 |
| G401, Cos-7, AZ-251 | Purified VacA | IP, CAA, FACS, WB | VacA receptor | 153 | ||
| RPTP-β | VacA | AZ-521 | Purified VacA | IP, FACS, PS, WB | VacA receptor | 28 |
| AZ-521, HL60, BHK-21 | Purified VacA | IP, CAA, FACS, PIS, WB | VacA receptor | 32 | ||
| RPTP-β−/− mice, primary cells, BHK-21 | Purified VacA | IHC, IFM, BBS, ASPAB, RT-PCR, WB | VacA receptor | 29 | ||
| TCR | Lpp20 | Mouse splenocytes, CD4+ T cells |
Synthetic peptides | FACS, TCPA, MHC restriction assay | Characterization of 2 CD4+ T cell epitopes of Lpp20 | 122 |
| HpaA | PBMCs, T cells, B cells, DCs | Synthetic peptides | FACS, TCPA, ELISPOT | Associated with reduced risk of severe gastric diseases | 123 | |
| UreB | PBMCs, T cells, B cells, DCs | Synthetic peptides | FACS, TCPA | Promising peptides for vaccine design | 124 | |
| TLR2 | LPS | Primary monocytes, HEK293, PECs | 43504, SS1, Astra 244 | Protein Array, ELISA | Activation of pro-inflammatory responses | 139 |
| MKN28, MKN48, THP1, T24, HEK293 | Clinical isolates | ELISA, FACS, LRGA, RT-PCR, WB | Activation of pro-inflammatory responses | 131 | ||
| HEK293, HEK-TLR2, HEK-TLR4 | Purified LPS samples | LGRA, ELISA, cDNA-MA,WB | Activation of pro-inflammatory responses | 138 | ||
| HSP-60 | NOMO1, U937 | 43504 | RPT, ASPAB, FACS, siRNA, ELISA, PIS, RT-PCR, WB | Activation of pro-inflammatory responses | 133 | |
| TLR4 | LPS | Guinea pig primary cells | 11637 | RT-PCR, ASPAB, WB | Activation of TLR4 and mitogen oxidase 1 | 154 |
| C57BL/6 mice, MKN1, human PBMCs | Purified LPS samples | TUA, ELISA | Low activity of LPS on TLR4 | 155 | ||
| HEK293, HEK-TLR2, HEK-TLR4 | J99, B128, X47 | MS, TLR-SA, MCA | Modification of LPS is crucial for host colonisation | 156 | ||
| TLR9 | DNA 5‘TTTAGGG |
BMDCs | Purified DNA oligos | ELISA | Importance of TLR-9 in the pathogenesis of IBD |
143 |
Abbreviations: AB, antibody; ABB, antibody blocking; ADAM, A disintegrin and metalloprotease; AhpC, Alkyl hydroperoxide reductase; AlpA/B, adherence-associated lipoproteins A/B; APCs, antigen presenting cells; ASPAB, activation specific phospho-antibody; BBS, biacore binding studies using surface plasmon resonance; BMDCs, bone marrow-derived cells; CAA, cell adhesion assay; Cag, proteins encoded by the cytotoxin-associated genes; CD, circular dichroism spectroscopy; CD18, cluster of differentiation 18; cDNA-MA, cDNA microarray; CMA, cell motility assay; CMIA, collagen type I and Matrigel invasion assays; CSA, cell spreading assay; CSLM, confocal laser scanning microscopy; CZG, casein zymography gel; DCs, dendritic cells; ErbB1–3, erythroblastic leukemia viral oncogene homologs in the EGFR family; EGFR, epidermal growth factor receptor; ELISA, enzyme-linked immunosorbent assay; ELISPOT, enzyme-linked immunosorbent spot; EMSA, electrophoretic mobility shift assay; FACS, fluorescence-activated cell sorting; FESEM, field emission scanning electron microscopy; GP130, glycoprotein 130; GPA, gentamicin protection assay; H,Kα, H, K–ATPAse α-subunit; HSP, eat shock protein; HtrA, high temperature requirement A; ICAM1, intracellular adhesion molecule 1; HPLC, high-pressure liquid chromatography; IBD, inflammatory bowel disease; ICA, in vitro cleavage assay; IFM, immunofluorescence microscopy; IHC, immunohistochemistry; ISGF3, interferon-stimulated gene factor 3; ImPC, immortalized primary cells; IP, immunoprecipitation; ISGF3, IFN-stimulated gene factor 3; JAK, janus kinase; KD, knockdown of genes; LCI, live cell imaging; LFA1, lymphocyte function-associated antigen 1; Lpp20, lipoprotein 20; LPS, lipopolysaccharide; LRGA, luciferase reporter gene assay; MCA, mouse colonization assay; MEF, mouse embryonic fibroblast; MHC-II, major histocompatibility group II; MS, mass spectrometry; NFAT, nuclear factor of activated T-cells; NMR, nuclear magnetic resonance spectroscopy; NOD, nucleotide-binding oligomerization domain; PAH, peptide array hybridization; PC, protein crystallization; PCA, peptide competition assays; PBMCs, peripheral blood mononuclear cells; PDA, pulldown assay; PECs, peritoneal exudate cells; PIS, pharmacological inhibitor studies; PS, peptide sequencing; RGAA, ras GTPase activation assay; RPT, recombinant protein techniques; RPTP, receptor protein tyrosine phosphatase; RT-PCR, real-time/reverse transcriptase PCR; Shp-2, SH2-containing protein phosphatase; shRNA, small hairpin RNA; siRNA, small interfering RNA; STAT3, signal transducer and activation of transcription 3; T4SS, type IV secretion system; TCPA, T-cell proliferation assay; TCR, T cell receptor; TLR, toll-like receptor; TLR-SA, TLR signaling assay; TUA, thymidine uptake assay; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; TWA, transwell assay; VacA, vacuolating cytotoxin A; WB, western blotting; Y2H, yeast two hybrid screening.