Ke-Ran Jia

CD4(+) T cell responses are critical for the pathogenesis of Helicobacter pylori infection. The present study evaluated the role of the Th17 subset in H. pylori infection. H. pylori infection induced significant expression of IL-17 and IFN-gamma in mouse gastric tissue. IL-23 and IL-12 were increased in the gastric tissue and in H. pylori-stimulated macrophages. Cell responses were examined by intracellular staining for IFN-gamma, IL-4, and IL-17. Mice infected with H. pylori developed a mixed Th17/Th1 response; Th17 responses preceded Th1 responses. Treatment of mice with an anti-IL-17 Ab but not a control Ab significantly reduced the H. pylori burden and inflammation in the stomach. H. pylori colonization and gastric inflammation were also lower in IL-17(-/-) mice. Furthermore, administration of recombinant adenovirus encoding mouse IL-17 increased both H. pylori load and inflammation. Further analysis showed that the Th1 cell responses to H. pylori were downregulated when IL-17 is deficient. These results together suggest that H. pylori infection induces a mixed Th17/Th1 cell response and the Th17/IL-17 pathway modulates Th1 cell responses and contributes to pathology.

Helicobacter pylori infection is a risk factor for development of peptic ulcers, and psychological stress (PS) may have a role in the pathogenesis of this condition. However, no interaction between PS and H. pylori infection (HI) has been established in the development of peptic ulcer, because colonization by H. pylori is the first step in the infection of the gastric mucosa, we examined H. pylori colonization of the stomach in BALB/c mice after PS. The mice were subjected to PS in a communication box test, in which they observed other mice experiencing a physical stressor (electrical) before they were inoculated with H. pylori. We found that the H. pylori colonization in the stomach of psychologically stressed mice was significantly greater than in the control mice (P < 0.05), and histological examination showed that the gastric mucosal injury in the stressed mice was more extensive than in the control mice (P < 0.05). To explore the underlying mechanisms, we administered RU486 (a type II glucocorticoid (GC) receptor antagonist) to antagonize the effect of endogenous corticosterone: this treatment decreased colonization by H. pylori in the psychologically stressed mice. We conclude that HI of the stomach of BALB/c mice is enhanced by PS, and the effect may be mediated by GCs.

Objective: Candida albicans is a common fungal pathogen that triggers complex host defense mechanisms, including coordinated innate and adaptive immune responses, to neutralize invading fungi effectively. Exploring the immune microenvironment has the potential to inform the development of therapeutic strategies for fungal infections. Methods: The study analyzed individual immune cell profiles in peripheral blood mononuclear cells from Candida albicans-infected mice and healthy control mice using single-cell transcriptomics, fluorescence quantitative PCR, and Western blotting. We investigated intergroup differences in the dynamics of immune cell subpopulation infiltration, pathway enrichment, and differentiation during Candida albicans infection. Results: Our findings indicate that infiltration of CD4 naive cells, regulatory T (Treg) cells, and Microtubules-associated (MT)-associated cells increased after infection, along with impaired T cell activity. Notably, CD4 T cells and plasma cells were enhanced after infection, suggesting that antibody production is dependent on T cells. In addition, we screened 6 hub genes, transcription factor forkhead box protein 3(Foxp3), cytotoxic T-lymphocyte associated protein 4 (CTLA4), Interleukin 2 Receptor Subunit Beta (Il2rb), Cd28, C-C Motif Chemokine Ligand 5 (Ccl5), and Cd27 for alterations associated with CD4 T cell differentiation. Conclusions: These results provide a comprehensive immunological landscape of the mechanisms of Candida albicans infection and greatly advance our understanding of adaptive immunity in fungal infections.