TLR2 Mediates Helicobacter pylori–Induced Tolerogenic Immune Response in MiceReportar como inadecuado

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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.

Autor: Xia Sun , Min Zhang , Mohamad El-Zataari, Stephanie Y. Owyang, Kathryn A. Eaton, Maochang Liu, Yu-Ming Chang, Weiping Zou, John Y



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