Interferon-γ promotes gastric lymphoid follicle formation but not gastritis in Helicobacter-infected BALB/c mice

Abstract

BackgroundMouse infection studies have shown that interferon-γ (IFN-γ), a T helper 1 (Th1) cytokine, is required for the development of severe pathology induced by chronic Helicobacter infection. This finding is largely based on studies performed using mice that have polarised Th1 responses i.e. C57BL/6 animals. The current work aims to investigate the role of IFN-γ in Helicobacter-induced inflammation in BALB/c mice which have Th2-polarised immune responses.ResultsAt 7 months post-infection with Helicobacter felis, IFN-γ deficiency in BALB/c mice had no significant effect on H. felis colonisation levels in the gastric mucosa, nor on humoral responses, or gastritis severity. Ifng −/− animals with chronic H. felis infection did, however, develop significantly fewer lymphoid follicle lesions, as well as increased IL-4 splenocyte responses, when compared with infected Ifng +/+ mice (P = 0.015 and P = 0.0004, respectively).ConclusionsThe work shows that in mice on a BALB/c background, IFN-γ is not required for bacterial clearance, antibody responses, nor gastric inflammation. Conversely, IFN-γ appears to play a role in the development of gastric lymphoid follicles, which are precursor lesions to mucosa-associated lymphoid tissue (MALT) lymphoma. This study highlights the importance of mouse host background on the susceptibility to Helicobacter-induced pathologies.

Other Helicobacters, gastric and gut microbiota

“…In line with what Bosschem et al. showed for H. suis , Chonwerawong et al . found that the host background has a profound impact on the susceptibility to Helicobacter‐induced pathologies.…”

“…Oral administration of alpha 5 defensin restored eubiosis and showed eradication of H. hepaticus. 38 Helicobacter bilis infection of C3H/HeN mice harboring the altered for H. suis, 34 Chonwerawong et al 46 found that the host background has a profound impact on the susceptibility to Helicobacter-induced pathologies. In a Th2-polarized BALB/c mouse model, the Th1 cytokine IFNγ was shown not to be required for host defense against experimental H. felis infection, although it was important for lymphoid aggregate formation.…”

Novel Insights of Lymphomagenesis of Helicobacter pylori-Dependent Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

“…Several studies with the H . species-infected animal models have demonstrated that IFN-γ can induce the formation of MALT, a precursor lesion of gastric MALT lymphoma [105,106]. However, IFN-γ also exhibits antitumor effects by producing NK cells, differentiating CD4 cells to Th1 cells, and activating the cytotoxicity of CD8+ cells [107,108].…”

Innate Immune Molecule NLRC5 Protects Mice From Helicobacter-induced Formation of Gastric Lymphoid Tissue

“…H felis does not form colonies on culture plates. 34 Although no significant differences in inflammatory responses were observed between WT and Nlrc5 mø-KO mice with H pylori infection, H felis-infected Nlrc5 mø-KO mice developed more severe inflammation and glandular hyperplasia when compared with WT animals (Figure 5C-F). A particularly noteworthy finding was that H felis-infected Nlrc5 mø-KO mice also developed significantly higher numbers of lymphoid structures or follicles within the gastric mucosa (Figure 5C-E), consisting of predominantly B220 þ cell populations and few CD3 þ T cells (Figure 5G).…”