IL-23 Contributes to Control of Chronic Helicobacter Pylori Infection and the Development of T Helper Responses in a Mouse Model1

Abstract

The immune response to Helicobacter pylori involves a mixed T helper-1, T helper-2, and T helper-17 response. It has been suggested that T helper cells contribute to the gastric inflammatory response during infection, and that T helper 1 (Th1) and T helper 17 (Th17) subsets may be required for control of H. pylori colonization in the stomach. The relative contributions of these subsets to gastritis and control of infection are still under investigation. IL-23 plays a role in stabilizing and expanding Th17 cell cytokine expression. Expression of IL-23, which is induced in dendritic cells and macrophages following co-culture with H. pylori, has also been reported to increase during H. pylori infection in humans and animal models. To investigate the role of IL-23 in H. pylori, we infected IL-23p19 deficient mice (IL-23−/−) and wild-type littermates with H. pylori strain SS1. At various time points post-infection, we assessed colonization, gastric inflammation, and cytokine profiles in the gastric tissue. Specifically, H. pylori-infected IL-23−/− mice have higher levels of H. pylori in their stomachs, significantly less chronic gastritis, and reduced expression of IL-17 and IFNγ compared to H. pylori-infected wild-type mice. While many of these differences were significant, the H. pylori infected IL-23−/− had mild increases in our measurements of disease severity. Our results indicate that IL-23 plays a role in the activation of the immune response and induction of gastritis in response to H. pylori by contributing to the control of infection and severity of gastritis.

Human-derived natural antibodies: biomarkers and potential therapeutics

“…The NAbs generated by B-1 cells bind to self-antigens such as oxidized lipids [37,38] and new antigens on apoptotic cells [39]. An increased incidence of autoimmune disorder occurs in gene-targeted mice that lack secreted IgMs.…”

Th1-Mediated Immunity against Helicobacter pylori Can Compensate for Lack of Th17 Cells and Can Protect Mice in the Absence of Immunization

“…IL-17 is present in biopsies of H. pylori -infected patients and mice, suggesting that IL-17 contributes to Helicobacter-associated pathology[21], [22], [23]. Two recent studies employing the IL-23 p19 KO mouse model have demonstrated a reduction in gastric pathology compared to wild type mice during chronic H. pylori infection[24], [25]. Our own observations demonstrate a significant increase of IL-17 following challenge of immunized mice, and a strong Th17 recall response in the T cells from immunized mice[10].…”

Helicobacter pylori Infection of the Gastric Mucosa

“…Whereas the role of IFN-γ in promoting inflammation is well established through the studies carried out in gene knockout mice, the role of IL-17 in promoting inflammation is less clear. Studies in mice lacking IL-17 (IL-17A −/− /IL-23p19 −/− ) report a dampened inflammation and reduced neutrophil infiltration during chronic H. pylori infection compared to wild-type mice, suggesting that IL-17 could promote inflammation through neutrophil recruitment (Shi et al, 2010;Horvath et al, 2012;Shiomi et al, 2008). Comprehensive studies of the IFN-γ and IL-17 levels in the stomach and the relation of these cytokines to inflammation and disease are currently lacking.…”