TLR2 Mediates Helicobacter pylori–Induced Tolerogenic Immune Response in Mice
Autor: | Kathryn A. Eaton, Weiping Zou, Min Zhang, Yu-Ming Chang, John Y. Kao, Xia Sun, Stephanie Y. Owyang, Mohamad El-Zataari, Maochang Liu |
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Rok vydání: | 2013 |
Předmět: |
lcsh:Medicine
T-Lymphocytes Regulatory Helicobacter Infections Immune tolerance Mice 03 medical and health sciences 0302 clinical medicine Immune system Species Specificity Immunity Immune Tolerance Animals lcsh:Science 030304 developmental biology Mice Knockout 0303 health sciences Multidisciplinary Innate immune system Helicobacter pylori biology CD11 Antigens Stomach lcsh:R Histocompatibility Antigens Class II Pattern recognition receptor FOXP3 Dendritic Cells Th1 Cells biology.organism_classification Toll-Like Receptor 2 3. Good health Mice Inbred C57BL TLR2 Gastritis Immunology Cytokines Th17 Cells Female lcsh:Q 030211 gastroenterology & hepatology Inflammation Mediators Research Article |
Zdroj: | PLoS ONE, Vol 8, Iss 9, p e74595 (2013) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | We have shown that Helicobacter pylori induces tolerogenic programming of dendritic cells and inhibits the host immune response. Toll-like receptors (TLRs) represent a class of transmembrane pattern recognition receptors essential for microbial recognition and control of the innate immune response. In this study, we examined the role of TLRs in mediating H. pylori tolerogenic programming of dendritic cells and their impact on anti–H. pylori immunity using C57BL/6 wild-type and TLR2-knockout (TLR2KO) mice. We analyzed the response of TLR2KO bone marrow-derived dendritic cells (BMDCs) to H. pylori SS1 stimulation and the outcome of chronic H. pylori infection in TLR2KO mice. We showed that H. pylori–stimulated BMDCs upregulated the expression of TLR2, but not TLR4, TLR5, or TLR9. H. pylori-stimulated BMDCs from TLRKO mice induced lower Treg and Th17 responses, but a higher IFN-γ response compared to H. pylori-stimulated BMDCs from wild-type mice. In vivo analyses following an H. pylori infection of 2 months duration showed a lower degree of gastric H. pylori colonization in TLR2KO mice and more severe gastric immunopathology compared to WT mice. The gastric mucosa of the infected TLR2KO mice showed a lower mRNA expression of Foxp3, IL-10, and IL-17A, but higher expression of IFN-γ compared to the gastric mRNA expression in infected wild-type mice. Moreover, the H. pylori–specific Th1 response was higher and the Treg and Th17 responses were lower in the spleens of infected TLR2KO mice compared to infected WT mice. Our data indicate that H. pylori mediates immune tolerance through TLR2-derived signals and inhibits Th1 immunity, thus evading host defense. TLR2 may be an important target in the modulation of the host response to H. pylori. |
Databáze: | OpenAIRE |
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