Overall, these and past studies dealing with the examination of H. pylori-derived effects on DCs suggest that local and monocyte-derived DC populations in the gastric mucosa may differ functionally and support conditions for a diverse population of T cells. It will require further studies, but by exploiting the murine model these intricate

relations may be dissectible. Th17 and Treg CD4+ cell subsets have been the focus of many recent immunologic studies on the course of Helicobacter infection. Regulatory T cells are thought to expand and eventually dominate in chronic infection hindering the function of protective T cells. Recent work is substantiating this scenario; for instance, Kindlund et al. [45] showed that eradication of H. pylori reduced Treg numbers, and Jang Everolimus cost et al. [46] reported increased numbers of Tregs in the stomachs of H. pylori-positive gastric cancer patients. Treg differentiation depends on TGF-β but, in the presence of IL-6, TGF-β rather promotes Th17. Th17 cells have become a new focus in this field because of their role in neutrophil recruitment and activation. Th17 thrive in particular when IL-1 and IL-23 are also present [47]. Shi et al. [48] confirmed the latter scenario after H. pylori infection of mice and found that Th17 and Th1 cells contribute to the overall pro-inflammatory T-cell response. Similar to other infection and autoimmune

disease models, Th17 and Th1 cells modulate each other. However, in the study by Shi et al., Th17 cells promoted an inflammatory component and Th1 response that correlated with higher H. pylori colonization when wild-type mice were compared with click here IL-17-deficient or normal mice treated with an anti-IL-17 antibody

just before infection. Similarly, IL-17, when delivered by recombinant 5-Fluoracil in vivo adenovirus just before H. pylori infection, increased inflammation and bacterial load 4 weeks later. These findings are at odds with work by Otani et al. [49], who observed an increase in gastritis and Th1 cytokines in mice treated with anti-IL-17 antibodies 6 months after infection. It also contradicts work by Kao et al. [44] who showed a negative correlation of IL-17 production and H. pylori burden. Complicating the issue further, Algood et al. [50] reported that mice deficient in the IL-17A receptor developed increased inflammation over a 6 -month time scale but also suffered tenfold increased bacterial burdens. Consistent with the model that IL-17 amplifies recruitment of neutrophils, the inflammatory infiltrate contained more lymphocytes, in particular B cells at the expense of granulocytes. In humans, serum levels of IL-17 seem to correlate with severity of disease; for instance, Jafarzadeh et al. [51] found increased levels of IL-17 in duodenal ulcer patients when compared to asymptomatic H. pylori-positive patients. Moreover, genetic typing for IL-17A alleles in over 800 individuals, 300 of which were gastric cancer patients, by Shibata et al.