BACKGROUND: Indoleamine 2,3 dioxygenase (IDO) interferes with immune responses. Host immune response against Helicobacter pylori is involved in the persistence of the infection and its related diseases. AIM: To investigate the role of IDO in the regulation of Th1/Th2 and Th17 pathways in H. pylori infection. METHODS: Gastric biopsy samples were taken from 42 patients who underwent endoscopy and evaluated for the expression of IDO by Western blotting. Gastritis was assessed by the Sydney system score. In a subgroup of patients, biopsies were treated with the IDO inhibitor 1-methyl-L-tryptophan and the expression of interferon-γ (IFN-γ) mRNA and that of T-bet, interleukin-17 (IL-17), and IL-4 determined by real-time PCR and Western blotting, respectively. RESULTS: IDO expression was found to be enhanced (p = .001) in gastric biopsies from H. pylori-infected (n = 18) compared with uninfected (n = 24) patients. Levels of IDO expression were inversely related to the gastritis score (r = -.684, p = .002) in H. pylori-infected gastric mucosa, but not in uninfected mucosa. In gastric biopsy cultures, IDO inhibition increased the expression of IFN-γ mRNA (p = .014), T-bet (p = .045), and IL-17 (p = .02) while decreasing that of IL-4 (p = .048). CONCLUSIONS: In H. pylori-infected human gastric mucosa, an enhanced expression of IDO is capable of modulating Th1/Th2 and Th17 pathways. This mechanism lowers gastric inflammation, possibly contributing to the persistence of H. pylori. Targeting the IDO pathway may be a new strategy for modulating H. pylori-induced mucosal immune response.
BACKGROUND: Indoleamine 2,3 dioxygenase (IDO) interferes with immune responses. Host immune response against Helicobacter pylori is involved in the persistence of the infection and its related diseases. AIM: To investigate the role of IDO in the regulation of Th1/Th2 and Th17 pathways in H. pylori infection. METHODS: Gastric biopsy samples were taken from 42 patients who underwent endoscopy and evaluated for the expression of IDO by Western blotting. Gastritis was assessed by the Sydney system score. In a subgroup of patients, biopsies were treated with the IDO inhibitor 1-methyl-L-tryptophan and the expression of interferon-γ (IFN-γ) mRNA and that of T-bet, interleukin-17 (IL-17), and IL-4 determined by real-time PCR and Western blotting, respectively. RESULTS:IDO expression was found to be enhanced (p = .001) in gastric biopsies from H. pylori-infected (n = 18) compared with uninfected (n = 24) patients. Levels of IDO expression were inversely related to the gastritis score (r = -.684, p = .002) in H. pylori-infected gastric mucosa, but not in uninfected mucosa. In gastric biopsy cultures, IDO inhibition increased the expression of IFN-γ mRNA (p = .014), T-bet (p = .045), and IL-17 (p = .02) while decreasing that of IL-4 (p = .048). CONCLUSIONS: In H. pylori-infected human gastric mucosa, an enhanced expression of IDO is capable of modulating Th1/Th2 and Th17 pathways. This mechanism lowers gastric inflammation, possibly contributing to the persistence of H. pylori. Targeting the IDO pathway may be a new strategy for modulating H. pylori-induced mucosal immune response.
Authors: A Velasco-Guardado; A Mora-Soler; L López-Corral; O López-Godino; L Vázquez-López; O Blanco-Muñez; E Pérez-López; A Rodríguez-Pérez; D Caballero-Barrigón Journal: Bone Marrow Transplant Date: 2016-03-07 Impact factor: 5.483
Authors: Anutthaman Parthasarathy; Penelope J Cross; Renwick C J Dobson; Lily E Adams; Michael A Savka; André O Hudson Journal: Front Mol Biosci Date: 2018-04-06
Authors: Felipe M Benavente; Jorge A Soto; Magdalena S Pizarro-Ortega; Karen Bohmwald; Pablo A González; Susan M Bueno; Alexis M Kalergis Journal: J Leukoc Biol Date: 2019-05-15 Impact factor: 4.962