Dual Faces of Immune Regulation: The Roles of Tregs and Bregs in <i>Helicobacter pylori</i> Infection and Therapeutic Implications

Background: Helicobacter pylori maintains life-long colonization even though it triggers a strong immune response. This phenomenon is mainly related to regulatory immune responses involving regulatory T cells (Tregs) and regulatory B cells (Bregs). These help in maintenance of immune tolerance but allow bacteria to survive.Methods: In this mini-review, existing data on immunoregulatory role of Tregs and Bregs in H. pylori infection are discussed, considering the cellular interactions, cytokine-mediated processes, impact on immune response and treatment prospects.Results: The FOXP3 Tregs down-regulate Th1 and Th17 immune responses through IL-10 and TGF-β production resulting in reduction of inflammatory response but blocking bacterial eradication. The IL-10 producing Bregs induce immune tolerance via inhibition of antigen presentation and expansion of Tregs, including Tr1 cells induction. Some new data suggest that regulation of the mentioned pathways, IL-10, TGF-β, PD-1/PD-L1 can increase chances of bacterial eradication and reduce adverse effects. Vaccines that target regulatory pathways in Tregs and Bregs also hold promise for the improvement of protective immunity.Conclusion: The Tregs and Bregs complement each other in the balance between the protection and tolerance during H. pylori infection. Better knowledge of this regulatory network will lead to targeted immunotherapy and improved vaccines.