L'infection par Helicobacter pylori et son éradication ne sont pas liées aux taux d'hémoglobine glyquée des jeunes diabétiques de type 1

ABSTRACTLewis (Le) antigens are fucosylated oligosaccharides present in theHelicobacter pylorilipopolysaccharide. Expression of these antigens is believed to be important forH. pyloricolonization, since Le antigens also are expressed on the gastric epithelia in humans. A galactosyltransferase encoded by β-(1,3)galTis essential for production of type 1 (Leaand Leb) antigens. The upstream genejhp0562, which is present in many but not allH. pyloristrains, is homologous to β-(1,3)galTbut is of unknown function. BecauseH. pyloridemonstrates extensive intragenomic recombination, we hypothesized that these two genes could undergo DNA rearrangement. A PCR screen and subsequent sequence analyses revealed that the two genes can recombine at both the 5′ and 3′ ends. Chimeric β-(1,3)galT-like alleles can restore function in a β-(1,3)galTnull mutant, but neither native nor recombinantjhp0562can. Mutagenesis ofjhp0562revealed that it is essential for synthesis of both type 1 and type 2 Le antigens. Transcriptional analyses of both loci showed β-(1,3)galTexpression in all wild-type (WT) and mutant strains tested, whereasjhp0562was not expressed injhp0562null mutants, as expected. Sincejhp0562unexpectedly displayed functions in both type 1 and type 2 Le synthesis, we asked whethergalT, part of the type 2 synthesis pathway, had analogous functions in type 1 synthesis. Mutagenesis and complementation analysis confirmed thatgalTis essential for Lebproduction. In total, these results demonstrate thatgalTandjhp0562have functions that cross the expected Le synthesis pathways and thatjhp0562provides a substrate for intragenomic recombination to generate diverse Le synthesis enzymes.

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Helicobacter pylori–binding nonacid glycosphingolipids in the human stomach

Journal of Biological Chemistry ◽

10.1074/jbc.ra118.004854 ◽

2018 ◽

Vol 293 (44) ◽

pp. 17248-17266 ◽

Cited By ~ 6

Author(s):

Chunsheng Jin ◽

Angela Barone ◽

Thomas Borén ◽

Susann Teneberg

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Structural Complexity ◽

Human Stomach ◽

Carbohydrate Binding ◽

Human Gastric Mucosa ◽

H Pylori ◽

Contrast Information

Helicobacter pylori has a number of well-characterized carbohydrate-binding adhesins (BabA, SabA, and LabA) that promote adhesion to the gastric mucosa. In contrast, information on the glycoconjugates present in the human stomach remains unavailable. Here, we used MS and binding of carbohydrate-recognizing ligands to characterize the glycosphingolipids of three human stomachs from individuals with different blood group phenotypes (O(Rh−)P, A(Rh+)P, and A(Rh+)p), focusing on compounds recognized by H. pylori. We observed a high degree of structural complexity, and the composition of glycosphingolipids differed among individuals with different blood groups. The type 2 chain was the dominating core chain of the complex glycosphingolipids in the human stomach, in contrast to the complex glycosphingolipids in the human small intestine, which have mainly a type 1 core. H. pylori did not bind to the O(Rh−)P stomach glycosphingolipids, whose major complex glycosphingolipids were neolactotetraosylceramide, the Lex, Lea, and H type 2 pentaosylceramides, and the Ley hexaosylceramide. Several H. pylori-binding compounds were present among the A(Rh+)P and A(Rh+)p stomach glycosphingolipids. Ligands for BabA-mediated binding of H. pylori were the Leb hexaosylceramide, the H type 1 pentaosylceramide, and the A type 1/ALeb heptaosylceramide. Additional H. pylori-binding glycosphingolipids recognized by BabA-deficient strains were lactosylceramide, lactotetraosylceramide, the x2 pentaosylceramide, and neolactohexaosylceramide. Our characterization of human gastric receptors required for H. pylori adhesion provides a basis for the development of specific compounds that inhibit the binding of this bacterium to the human gastric mucosa.

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Helicobacter pylori and Glycemia Control in Children with Type 1 Diabetes: Response to Treatment

Pediatric Research ◽

10.1203/00006450-199904020-00504 ◽

1999 ◽

Vol 45 (4, Part 2 of 2) ◽

pp. 85A-85A

Author(s):

Rodolfo E Begue ◽

Ricardo Gomez ◽

Terry Compton ◽

Alfonso Vargas

Keyword(s):

Type 1 Diabetes ◽

Helicobacter Pylori ◽

Response To Treatment

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Influence of monoclonal anti-Lewis b, anti-H type 1, and anti-sialyl Lewis x antibodies on binding of Helicobacter pylori to MUC1 mucin

Molecular and Cellular Biochemistry ◽

10.1007/s11010-013-1833-1 ◽

2013 ◽

Vol 385 (1-2) ◽

pp. 249-255 ◽

Cited By ~ 2

Author(s):

I. Radziejewska ◽

K. Leszczyńska ◽

M. Borzym-Kluczyk

Keyword(s):

Helicobacter Pylori ◽

Sialyl Lewis X ◽

Lewis X ◽

Muc1 Mucin ◽

Sialyl Lewis

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Lack of humoral response against Helicobacter pylori peptides homologous to human ZnT8 in Hashimoto’s thyroiditis patients

The Journal of Infection in Developing Countries ◽

10.3855/jidc.6284 ◽

2015 ◽

Vol 9 (06) ◽

pp. 631-634 ◽

Cited By ~ 3

Author(s):

Speranza Masala ◽

Davide Cossu ◽

Magdalena Niegowska ◽

Giuseppe Mameli ◽

Daniela Paccagnini ◽

...

Keyword(s):

Helicobacter Pylori ◽

Hashimoto’S Thyroiditis ◽

Molecular Mimicry ◽

Humoral Response ◽

Hashimoto's Thyroiditis ◽

Enzyme Linked Immunosorbent Assay ◽

Mycobacterium Avium Subsp Paratuberculosis ◽

Humoral Responses ◽

Self Antigen

Introduction: The Helicobacter pylori (HP) reinfection rate seems to be higher in developing countries than in developed ones. An increased seroprevalence of HP has also been reported in patients with type 1 diabetes (T1D) and Hashimoto’s thyroiditis (HT). Mycobacterium avium subsp. paratuberculosis (MAP) has been linked to both T1D and HT. Quite a few lines of evidence indicate that autoantibodies against several epitopes belonging to human zinc transporter 8 (ZnT8) cross-recognize the homologous MAP3865c epitopes in both T1D and HT patients. HP may play a role in HT disease, most likely acting through a molecular mimicry mechanism that targets ZnT8 as reported for MAP and the two autoimmune diseases. Methodology: An enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of antibodies against several epitopes deriving from HP proteins, which are highly homologous to the immunodominant ZnT8 peptides previously identified: ZnT8178–186 and ZnT8186–194. Results: None of the HP peptides tested were significantly recognized when the humoral responses of 92 HT patients and 91 healthy volunteers were analyzed. Conclusions: These findings do not support a triggering role for HP (through ZnT8 mimicking) in HT. If a molecular mimicry phenomenon is taking place, it involves a different self-antigen. Moreover, the negative outcome of the experiments performed stresses the fact that sharing stretches of sequence homology is relevant, but not enough to trigger an antibody-mediated cross-recognition.

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Effect of Helicobacter pylori Eradication in the Glycemia of Children With Type 1 Diabetes

Southern Medical Journal ◽

10.1097/00007611-200208000-00011 ◽

2002 ◽

Vol 95 (8) ◽

pp. 842-845 ◽

Cited By ~ 10

Author(s):

RODOLFO E. BÉGUÉ ◽

RICARDO GÓMEZ ◽

TERRY COMPTON ◽

ALFONSO VARGAS

Keyword(s):

Type 1 Diabetes ◽

Helicobacter Pylori ◽

Helicobacter Pylori Eradication

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Helicobacter pylori Disrupts STAT1-Mediated Gamma Interferon-Induced Signal Transduction in Epithelial Cells

Infection and Immunity ◽

10.1128/iai.72.1.537-545.2004 ◽

2004 ◽

Vol 72 (1) ◽

pp. 537-545 ◽

Cited By ~ 20

Author(s):

David J. Mitchell ◽

Hien Q. Huynh ◽

Peter J. M. Ceponis ◽

Nicola L. Jones ◽

Philip M. Sherman

Keyword(s):

Helicobacter Pylori ◽

Epithelial Cells ◽

Tyrosine Phosphorylation ◽

Nuclear Translocation ◽

Gamma Interferon ◽

Cell Protein ◽

Stat1 Signaling ◽

Ifn Γ ◽

H Pylori

ABSTRACT Infection with Helicobacter pylori is chronic despite a vigorous mucosal immune response characterized by gastric T-helper type 1 cell expansion and gamma interferon (IFN-γ) production. IFN-γ signals by activation and nuclear translocation of signal transducer and activator of transcription 1 (STAT1); however, the effect of H. pylori infection on IFN-γ-STAT1 signaling is unknown. We infected human gastric (MKN45 and AGS) and laryngeal (HEp-2) epithelial cell lines with type 1 and type 2 H. pylori strains and then stimulated them with IFN-γ. Western blotting of whole-cell protein extracts revealed that infection with live, but not heat-killed, H. pylori time-dependently decreased IFN-γ-induced STAT1 tyrosine phosphorylation. Electrophoretic mobility shift assay of nuclear protein extracts demonstrated that H. pylori infection reduced IFN-γ-induced STAT1 DNA binding. STAT1 was unable to translocate from the cytoplasm to the nucleus in H. pylori-infected HEp-2 cells examined by immunofluorescence, and reverse transcription-PCR showed that IFN-γ-induced interferon regulatory factor 1 expression was inhibited. These effects were independent of the cagA, cagE, and VacA status of the infecting H. pylori strain. Furthermore, neither H. pylori culture supernatants nor conditioned medium from H. pylori-infected MKN45 cells inhibited IFN-γ-induced STAT1 tyrosine phosphorylation, suggesting that inhibition is independent of a soluble epithelial or bacterial factor but is dependent on bacterial contact with epithelial cells. H. pylori disruption of IFN-γ-STAT1 signaling in epithelial cells may represent a mechanism by which the bacterium modifies mucosal immune responses to promote its survival in the human host.

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Effect of Helicobacter pylori Eradication in the Glycemia of Children With Type 1 Diabetes

Southern Medical Journal ◽

10.1097/00007611-200295080-00012 ◽

2002 ◽

Vol 95 (8) ◽

pp. 842-845 ◽

Cited By ~ 5

Author(s):

RODOLFO E. BÉGUÉ ◽

RICARDO GÓMEZ ◽

TERRY COMPTON ◽

ALFONSO VARGAS

Keyword(s):

Type 1 Diabetes ◽

Helicobacter Pylori ◽

Helicobacter Pylori Eradication

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