Chemokines and antimicrobial peptides have a cag-dependent early response to Helicobacter pylori infection in primary human gastric epithelial cells.
Helicobacter pylori infection systematically causes chronic gastric inflammation that can persist asymptomatically or evolve toward more severe gastroduodenal pathologies, such as ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. The cag pathogenicity island (cag PAI) of H. pylori allows translocation of the virulence protein CagA and fragments of peptidoglycan into host cells, thereby inducing production of chemokines, cytokines, and antimicrobial peptides. In order to characterize the inflammatory response to H. pylori, a new experimental protocol for isolating and culturing primary human gastric epithelial cells was established using pieces of stomach from patients who had undergone sleeve gastrectomy. Isolated cells expressed markers indicating that they were mucin-secreting epithelial cells. Challenge of primary epithelial cells with H. pylori B128 underscored early dose-dependent induction of expression of mRNAs of the inflammatory mediators CXCL1 to -3, CXCL5, CXCL8, CCL20, BD2, and tumor necrosis factor alpha (TNF-α). In AGS cells, significant expression of only CXCL5 and CXCL8 was observed following infection, suggesting that these cells were less reactive than primary epithelial cells. Infection of both cellular models with H. pylori B128ΔcagM, a cag PAI mutant, resulted in weak inflammatory-mediator mRNA induction. At 24 h after infection of primary epithelial cells with H. pylori, inflammatory-mediator production was largely due to cag PAI substrate-independent virulence factors. Thus, H. pylori cag PAI substrate appears to be involved in eliciting an epithelial response during the early phases of infection. Afterwards, other virulence factors of the bacterium take over in development of the inflammatory response. Using a relevant cellular model, this study provides new information on the modulation of inflammation during H. pylori infection.
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France.
Pascale
P
Mustapha
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
Isabelle
I
Paris
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
Magali
M
Garcia
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
Cong Tri
CT
Tran
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
Julie
J
Cremniter
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
Martine
M
Garnier
Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
Jean-Pierre
JP
Faure
Polyclinique de Poitiers, Poitiers, France.
Thierry
T
Barthes
Institut Pasteur, Unité de Biologie et Génétique de la Paroi Bactérienne, Paris, France INSERM, Equipe Avenir, Paris, France.
Ivo G
IG
Boneca
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France.
Franck
F
Morel
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
Jean-Claude
JC
Lecron
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
Christophe
C
Burucoa
Laboratoire Inflammation, Tissus Epithéliaux et Cytokines (LITEC-EA 4331), Université de Poitiers, Poitiers, France charles.bodet@univ-poitiers.fr.
Charles
C
Bodet
D000942:Antigens, Bacterial / Q000276:immunology; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology*; D044404:Genomic Islands; D016480:Helicobacter pylori / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D013270:Stomach / Q000166:cytology*
D000942:Antigens, Bacterial; D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D018925:Chemokines; C080866:cagA protein, Helicobacter pylori