Extracellular and intracellular pattern recognition receptors cooperate in the recognition of Helicobacter pylori
| Autor: | Jörg Mages, Roland Lang, Christian Prinz, Lena Rad, Petra Voland, Roland Rad, Katharina Eisenächer, Roland M. Schmid, Ruth Ferstl, Carsten J. Kirschning, Wibke Ballhorn, Anne Krug, Hermann Wagner, Stefan Bauer |
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| Rok vydání: | 2008 |
| Předmět: |
DNA
Bacterial Population Antigen-Presenting Cells Enzyme-Linked Immunosorbent Assay Biology Sensitivity and Specificity Helicobacter Infections Mice Animals education Cells Cultured Mice Knockout Toll-like receptor education.field_of_study Innate immune system Hepatology Helicobacter pylori Gene Expression Profiling Toll-Like Receptors Gastroenterology Pattern recognition receptor Dendritic cell Dendritic Cells Flow Cytometry Immunity Innate Cell biology Human morbidity Mice Inbred C57BL TLR2 RNA Bacterial Gene Expression Regulation TRIF Receptors Pattern Recognition Immunology Models Animal Signal Transduction |
| Zdroj: | Gastroenterology. 136(7) |
| ISSN: | 1528-0012 |
| Popis: | Background & Aims Helicobacter pylori infects half of the world's population, thereby causing significant human morbidity and mortality. The mechanisms by which professional antigen-presenting cells recognize the microbe are poorly understood. Methods Using dendritic cells (DCs) from TRIF, MyD88, TLR 2/4/7/9 −/− , and multiple double/triple/quadruple mutant mice, we characterized receptors and pathways mediating innate immune recognition of H pylori . Results We identified a MyD88-dependent component of the DC activation program, which was induced by surface TLRs, with TLR2 and to a minor extent also TLR4 being the exclusive surface receptors recognizing H pylori . A second MyD88-dependent component could be blocked in TLR2/4 −/− DCs by inhibitors of endosomal acidification and depended on intracellular TLRs. We identified TLR9-mediated recognition of H pylori DNA as a principal H pylori –induced intracellular TLR pathway and further showed that H pylori RNA induces proinflammatory cytokines in a TLR-dependent manner. Microarray analysis showed complementary, redundant, and synergistic interactions between TLRs and additionally revealed gene expression patterns specific for individual TLRs, including a TLR2-dependent anti-inflammatory signature. A third component of the DC activation program was primarily composed of type I interferon-stimulated genes. This response was MyD88 and TRIF independent but was inducible by RIG-I–dependent recognition of H pylori RNA. Conclusions These results provide novel comprehensive insights into the mechanisms of H pylori recognition by DCs. Understanding these processes provides a basis for the rational design of new vaccination strategies. |
| Databáze: | OpenAIRE |
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