Male-Dependent Promotion of Colitis in 129 Rag2−/− Mice Co-Infected with Helicobacter pylori and Helicobacter hepaticus

Abstract

The prevalence of gastric Helicobacter pylori (Hp) infection is ~50% of the world population. However, how Hp infection influences inflammatory bowel disease in humans is not fully defined. In this study, we examined whether co-infection with Hp influenced Helicobacter hepaticus (Hh)–induced intestinal pathology in Rag2−/− mice. Rag2−/− mice of both sexes were infected with Hh, of which a subgroup was followed by infection with Hp two weeks later. Co-infected males, but not females, had significantly higher total colitis index scores in the colon at both 10 and 21 weeks post-Hh infection (WPI) and developed more severe dysplasia at 21 WPI compared with mono-Hh males. There were no significant differences in colonization levels of gastric Hp and colonic Hh between sexes or time-points. In addition, mRNA levels of colonic Il-1β, Ifnγ, Tnfα, Il-17A, Il-17F, Il-18, and Il-23, which play important roles in the development and function of proinflammatory innate lymphoid cell groups 1 and 3, were significantly up-regulated in the dually infected males compared with mono-Hh males at 21 WPI. These data suggest that concomitant Hp infection enhances the inflammatory responses in the colon of-Hh-infected Rag2−/− males, which results in more severe colitis and dysplasia.

Selenium-Enriched Black Soybean Protein Prevents Benzo(a)pyrene-Induced Pyroptotic Colon Damage and Gut Dysbacteriosis

“…The increase of Helicobacter and Desulfovibrio has been related to the colitis, and a member of Desulfovibrio could produce endotoxins and toxic sulfur, thereafter inducing inflammation. 59,60 As expected, the results from the integrative analysis demonstrate strong connections between beneficial effects of SeBSP on alleviating BaP-impaired metabolic enzymes, pyroptosis indexes, oxidative and inflammatory factors, and those heath-relevant bacterial taxa. In addition, BaP remarkably increased Akkermansia, which was then reduced by SeBSP.…”

The Effect of Sex-Specific Differences on IL-10−/− Mouse Colitis Phenotype and Microbiota

“…Similar sexual dimorphism was described in the less used IBD model 129 Rag2 −/− mice [24]. In this scenario, however, the concomitant infection of Helicobacter pylori enhanced the colonic inflammatory response in males, resulting in more severe colitis and dysplasia compared with females [24]. We must remark that the fecal lipocalin-2 levels (Figure 2A), used as a non-invasive inflammatory marker, did not show significant differences between males and females.…”

“…Indeed, authors reported more severe intestinal inflammation in female mice compared to males, but only by histological injury score and colonic interferon-gamma (IFNγ) secretion. Similar sexual dimorphism was described in the less used IBD model 129 Rag2 −/− mice [ 24 ]. In this scenario, however, the concomitant infection of Helicobacter pylori enhanced the colonic inflammatory response in males, resulting in more severe colitis and dysplasia compared with females [ 24 ].…”

The Roles of Innate Lymphoid Cells in the Gastric Mucosal Immunology and Oncogenesis of Gastric Cancer

“…Secretion of cytokines such as IFN-γ by group 1 ILCs and NCR-ILC3s could contribute to the clearance of intracellular bacteria via promoting activation and phagocytosis by macrophages and dendritic cells [ 16 ]. Meanwhile, the IL-22 production by group 3 ILCs could further induce the production of multiple anti-microbial peptides, such as defensins and cathelicidins from epithelial cells [ 25 , 64 ], as well as RegIIIγ from both epithelial cells and ILC3s [ 65 , 66 , 67 ]. In addition, ILCs are also proposed to be directly involved in regulating gut epithelial integrity [ 16 ].…”