Research articleIncreased Indoleamine 2, 3-Dioxygenase expression modulates Th1/Th17/Th22 and Treg pathway in humans with Helicobacter Pylori-Infected gastric mucosa
Introduction
Indoleamine 2,3 dioxgenase (IDO) is an inducible enzyme that can mediate the degradation of tryptophan (Trp) [1]. Also, IDO is widely expressed in various cells such as epithelial cells, endothelial cells, macrophages, dendritic cells (DC), and tumor cells [2], [3], [4]. IDO expression is known to be induced by various stimuli including pathogen-associated molecular patterns (PAMP), co-stimulatory molecules, and inflammatory cytokines such as interferon gamma (INF-γ) [2]. The biologic function of the IDO enzyme is to be contributed to the control of inflammation and takes part in creation of acquired peripheral tolerance [5]. Also, IDO can enhance the tissue-reparative effects of inflammation while limiting the tissue-destructive effects [6]. Helicobacter pylori (H. pylori) is one of the most common human pathogens, it is estimated that 50 percent of the world population is infected by this bacterium [7]. However, 80 percent of the infected people are asymptomatic, 10 to 20 percent of them will show developed peptic ulcers diseases (PUD), and about 1 to 2 percent stomach cancer (gastric cancer) [8]. The variable outcomes of H. pylori infection likely depend on various factors such as bacterial virulence factors, genetic interaction, types of immune responses (innate and adaptive immune responses), and environmental factors [9], [10], [11]. Deaths from PUD (gastric and duodenal ulcers) in the last centuries have been dramatic [12]. However, the main mechanism of PUD that is caused by H. pylori infection, is not fully understood yet, but no treatment for a chronic systemic inflammatory in the H. pylori infected subjects is assumed that play an important role in gastric epithelial damage [13]. H. pylori infection can cause many local inflammations at the site of infection [14]. For example, increased IL-10+CD19+ B cells and T helper (Th) lymphocytes such as Th1, Th17, Th22, and T regulator (Treg) cells in the H. pylori infected patients can be considered as a main role in the pathogenesis of this infection [15], [16], [17], [18]. Since IDO protein expression in different clinical outcomes (such as gastritis and PUD) and its association with the number of Th1, Th17, Th22, and Treg lymphocytes in patients with H. pylori infection has not been investigated up to now. Therefore, the purpose of this research was to investigate the correlation between IDO protein expression with the number of Th1, Th17, Th22, Treg lymphocytes, and different clinical results in the infected patients.
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Patients and sampling
Four antral biopsies specimens were collected from 150 patients who underwent upper gastrointestinal endoscopy at Hajar Hospital, Shahrekord, Iran, for symptoms of indigestion: rapid urease test (RUT), histological analysis, polymerase chain reaction (PCR) test and IDO protein analysis. Then, patients were classified as H. pylori-positive subjects with gastritis (n = 55: 26 males, 29 females; mean age: 50.18 ± 15.02 years old), H. pylori-positive subjects with PUD (n = 47: 27 males, 20 females;
Study population
Demographic characterization of infected and uninfected patients was showed in Table 2. The relationship between the type of diseases and gender/age in our study population was not significant.
Enhanced IDO protein expression in gastric mucosa of H. pylori-positive subjects
IDO protein expression was evaluated using WB in protein extracts of freshly collected biopsies (Fig. 1A). We observed that, H. pylori-positive subjects considerably had higher IDO protein expression compared to H. pylori-negative subjects (Fig. 1B; P < 0.0001). The fold changes in IDO protein expression
Discussion
Most H. pylori-positive subjects indicate asymptomatic chronic inflammation, however some of the subjects indicate severe gastritis diseases and PUD [21]. In this study, we first confirmed that, H. pylori-positive subjects had significantly higher IDO protein expression than H. pylori-negative subjects. Additionally, H. pylori-positive subjects with gastritis disease had much higher IDO protein expression than H. pylori-positive subjects with PUD. In support of this finding, Larussa et al. [22]
Conclusion
The results in this research suggest that Th1, Th17, Th22, and Treg cell immune responses during H. pylori infection have been prominently altered by IDO protein, which in turn represents an important risk factor for PUD development.
Statement of ethics
This study was approved by the ethical board of Shahrekord University of medical sciences with number: IR.SKUMS.REC.1394.28. Informed consent was obtained from each volunteer before participation. The authors have no ethical conflicts to disclose.
Disclosure statement
This manuscript was approved by all authors. No competing interests declared.
Funding sources
This study was financially supported by research deputy of Shahrekord University of Medial Sciences with grant number 2043.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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