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- W2032770805 abstract "Aims: Helicobacter pylori leads to a chronic inflammation of the gastric mucosa, but mechanisms of immune response are poorly understood. Recognition of infection leads to induction of adaptive immunity through activation of antigen-presenting cells (APCs). Among APCs, dendritic cells (DCs) have the unique capacity to deliver antigens from the periphery to T cells in secondary lymphoid organs. Methods: We analyzed molecular mechanisms of the H. pylori-induced APC-activation in vitro and investigated the influence of Myd88-signalling on the phenotype of adaptive immunity to H. pylori in a murine infection model. Results: The adaptor protein Myd88 mediates Toll-like receptor (TLR), IL-1 and IL-18 signalling. DCs from wild-type, IL-1R-/- and IL-18-/- mice responded to H. pylori with secretion of proinflammatory cytokines and upregulation of MHC-II and costimulatory molecules. In Myd88-/- DCs these processes were profoundly impaired, demonstrating that TLR-dependent H. pylori-sensing affects DC activation. Analysis of the H. pylori-specific DC-transcriptome revealed that large parts of the bacteria-induced transcriptional changes depended on Myd88-signalling, comprising numerous genes involved in crucial steps of immune regulation, such as dendritic cell maturation/differentiation, antigen uptake/presentation, and effector cell recruitment/activation. The impaired ability of Myd88-/- DCs, B cells and macrophages to mount a proinflammatory response to H. pylori in vitro was reflected in vivo by reduced gastric inflammation and increased bacterial colonisation in Myd88-deficient mice. Furthermore, Helicobacter-specific IgG2c/IgG1 ratios were reduced in Myd88-/- animals, suggesting the involvement of the Myd88-dependent pathway in the instruction of adaptive immunity toward a Th1 phenotype. Conclusion: A principal pathway by which DCs sense H. pylori and become activated is the TLR-dependent signalling cascade. In vivo, Myd88-signalling affects adaptive immunity to the bacterium." @default.
- W2032770805 created "2016-06-24" @default.
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- W2032770805 date "2007-08-01" @default.
- W2032770805 modified "2023-09-27" @default.
- W2032770805 title "Toll-like receptor dependent activation of antigen presenting cells affects adaptive immunity to Helicobacter pylori" @default.
- W2032770805 doi "https://doi.org/10.1055/s-2007-988329" @default.
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