Helicobacter pylori-Mediated Protection from Allergy Is Associated with IL-10-Secreting Peripheral Blood Regulatory T Cells

Abstract

Helicobacter pylori infections are usually established in early childhood and continuously stimulate immunity, including T-helper 1 (Th1), Th17, and regulatory T-cell (Treg) responses, throughout life. Although known to be the major cause of peptic ulcer disease and gastric cancer, disease occurs in a minority of those who are infected. Recently, there has been much interest in beneficial effects arising from infection with this pathogen. Published data robustly show that the infection is protective against asthma in mouse models. Epidemiological studies show that H. pylori is inversely associated with human allergy and asthma, but there is a paucity of mechanistic data to explain this. Since Th1 and Treg responses are reported to protect against allergic responses, we investigated if there were links between the human systemic Th1 and Treg response to H. pylori and allergen-specific IgE levels. The human cytokine and T-cell responses were examined using peripheral blood mononuclear cells (PBMCs) from 49 infected and 58 uninfected adult patients. Concentrations of total and allergen-specific plasma IgE were determined by ELISA and ImmunoCAP assays. These responses were analyzed according to major virulence factor genotypes of the patients’ colonizing H. pylori strains. An in vitro assay was employed, using PBMCs from infected and uninfected donors, to determine the role of Treg cytokines in the suppression of IgE. Significantly higher frequencies of IL-10-secreting CD4+CD25hi Tregs, but not H. pylori-specific Th1 cells, were present in the peripheral blood of infected patients. Total and allergen-specific IgE concentrations were lower when there was a strong Treg response, and blocking IL-10 in vitro dramatically restored IgE responses. IgE concentrations were also significantly lower when patients were infected with CagA+ strains or those expressing the more active i1 form of VacA. The systemic IL-10+ Treg response is therefore likely to play a role in H. pylori-mediated protection against allergy in humans.

Helicobacter pylori controls NLRP3 expression by regulating hsa-miR-223-3p and IL-10 in cultured and primary human immune cells

“…7 In contrast, persistent infection of H. pylori has also been found to be beneficial for the human host by suppressing other illnesses, including asthma, allergies and inflammatory bowel disease. [8][9][10][11] Host gene polymorphisms play a crucial role in producing different associated pathologies of H. pylori infection. Among these, a specific IL-1b gene polymorphism has prominence and was directly related to gastric cancer development.…”

Association between infection with Helicobacter pylori and atopy in young Ethiopian children: A longitudinal study

“…Infection with these strains reportedly induces a higher‐level T‐helper 1 (Th1) cellular immune response, which may counterbalance the pro‐allergic Th2 response. CagA+ strains usually also co‐express the most active form of the vacuolating cytotoxin A (VacA), and this is important in the induction of immunosuppressive regulatory T cell (Treg) responses . Higher frequencies of IL‐10‐secreting Tregs were shown to be present in the peripheral blood of H. pylori‐ infected patients in the UK, and serum IgE concentrations were lowest when there was a strong Treg response.…”

“…Higher frequencies of IL‐10‐secreting Tregs were shown to be present in the peripheral blood of H. pylori‐ infected patients in the UK, and serum IgE concentrations were lowest when there was a strong Treg response. Mechanistic in vitro experiments showed that the systemic IL‐10+ Treg response is likely to play an important role in H. pylori ‐mediated protection against allergy in humans . A number of studies with mouse models of allergy and asthma have very convincingly demonstrated that H. pylori infection is protective and that VacA‐induced Tregs play a major role .…”

Inflammation, immunity, and vaccines for Helicobacter pylori infection

“…These findings are very interesting in the context of the study by Kienesberger et al., showing that H. pylori influences the microbiota and host immune responses not only locally in the stomach, but also within the lung. In addition, an increased frequency of IL‐10‐producing CD4 + CD25 hi Treg in the peripheral blood of H. pylori ‐infected, nonallergic/atopic individuals has been associated with reduced plasma IgE concentrations . Of note, differences in total IgE according to the virulence genotype of the colonizing H. pylori strains were observed.…”