Reduced colonization of gastric mucosa by Helicobacter pylori in mice deficient in interleukin‐10 1

Yan²,

Proc. Natl. Acad. Sci. U.S.A.

et al. 2010

134

152

Olfactomedin 4 (OLFM4) is a glycoprotein that has been found to be up-regulated in inflammatory bowel diseases and Helicobacter pylori infected patients. However, its role in biological processes such as inflammation or other immune response is not known. In this study, we generated OLFM4 KO mice to investigate potential role(s) of OLFM4 in gastric mucosal responses to H. pylori infection. H. pylori colonization in the gastric mucosa of OLFM4 KO mice was significantly lower compared with WT littermates. The reduced bacterial load was associated with enhanced infiltration of inflammatory cells in gastric mucosa. Production and expression of proinflammatory cytokines/chemokines such as IL-1β, IL-5, IL-12 p70, and MIP-1α was increased in OLFM4 KO mice compared with infected controls. Furthermore, we found that OLFM4 is a target gene of NF-κB pathway and has a negative feedback effect on NF-κB activation induced by H. pylori infection through a direct association with nucleotide oligomerization domain-1 (NOD1) and -2 (NOD2). Together these observations indicate that OLFM4 exerts considerable influence on the host defense against H. pylori infection acting through NOD1 and NOD2 mediated NF-κB activation and subsequent cytokines and chemokines production, which in turn inhibit host immune response and contribute to persistence of H. pylori colonization.NF-κB | nucleotide oligomerization domain-1 and -2

Section: Discussionsupporting

confidence: 55%

Olfactomedin 4 down-regulates innate immunity against Helicobacter pylori infection

Yan²,

Proc. Natl. Acad. Sci. U.S.A.

et al. 2010

134

152

The Journal of Immunology

“…This shifts the Th1/Th2 immune balance, and the immunosuppressive nature of these cells can lead to tolerance against tumor Ags or pathogens (43,44). IL-10 2/2 mice, compared with wild-type mice, develop severe gastritis when infected with H. pylori bacteria; therefore, IL-10 may have a potential role in downregulating H. pylori-induced inflammation at the site of infection (45). However, we did not use H. pylori bacteria to stimulate DCs, but only HP-NAP, and did not observe IL-10 secretion from NAPDC, when cultured in the presence of tumor cell supernatant during the maturation process.…”

Section: Discussionmentioning

confidence: 99%

Vector-Encoded Helicobacter pylori Neutrophil-Activating Protein Promotes Maturation of Dendritic Cells with Th1 Polarization and Improved Migration

Ramachandran

Jin

et al. 2014

Helicobacter pylori neutrophil-activating protein (HP-NAP) is a major virulence factor involved in H. pylori infection. Both HP-NAP protein and oncolytic viruses encoding HP-NAP have been suggested as immunotherapeutic anticancer agents and adjuvants for vaccination but with little known about its mode of action to activate adaptive immunity. Dendritic cells (DCs) are key players in bridging innate and adaptive immune responses, and in this study we aim to evaluate the effect of HP-NAP on DC maturation, migration, and induction of adaptive immune response. Maturation markers CD83, CD80, CD86, HLA-DR, CD40, and CCR7 were upregulated on human DCs after treatment with supernatants from HP-NAP adenovirus–infected cells. HP-NAP–activated DCs had a Th1 cytokine secretion profile, with high IL-12 and relatively low IL-10 secretion, and migrated toward CCL19. Ag-specific T cells were efficiently expanded by Ag-presenting HP-NAP–activated DCs, which is an important property of functionally mature DCs. Furthermore, intradermal injections of HP-NAP–encoding adenovirus in C57BL/6 mice enhanced resident DC migration to draining lymph nodes, which was verified by imaging lymph nodes by two-photon microscopy and by phenotyping migrating cells by flow cytometry. In conclusion, therapeutic effects of HP-NAP are mediated by maturation of DCs and subsequent activation of Ag-specific T cells in addition to provoking innate immunity.

Microbiology and Immunology

“…Chen et al reported significantly reduced colonization of the gastric mucosa in IL-10-deficient mice so that IL-10 seemed to be an inhibitor of the protective immune response to H. pylori infection (6). Thus, a role of Th1 type response may be important in the pathogenesis of H. pylori-associated disease.…”

Section: Discussionmentioning

confidence: 99%

Role of Tumor Necrosis Factor‐Alpha and Interferon‐Gamma in Helicobacter pylori Infection

Yamamoto

Kita

Ohno

et al. 2004

Immune responses to Helicobacter pylori infection play important roles in gastroduodenal diseases. The contributions of tumor necrosis factor‐α (TNF‐α) and interferon‐7 (IFN‐γ) to the induction of gastric inflammation and to the protection from H. pylori infection were investigated using TNF‐α gene‐knockout (TNF‐α−/−) mice and IFN‐γ gene‐knockout (IFN‐γ−/−) mice. We first examined the colonizing ability of H. pylori strain CPY2052 in the stomach of C57BL/6 wild‐type and knockout mice. The number of H. pylori colonized in the stomach of IFN‐γ−/− and TNF‐α−/− mice was higher than that of wild‐type mice. These findings suggest that TNF‐α and IFN‐γ may play a protective role in H pylori infection. Furthermore, we examined the contribution of TNF‐α and IFN‐γ to gastric inflammation. The CPY2052‐infected TNF‐α−/− mice showed a moderate infiltration of mononuclear cells in the lamina propria and erosions in the gastric epithelium as did wild‐type mice, whereas the CPY2052‐infected IFN‐γ−/− mice showed no inflammatory findings even 6 months after infection. These results demonstrate that IFN‐γ may play an important role in gastric inflammation induced by H. pylori infection, whereas TNF‐α may not participate in the development of inflammatory response.