Extracellular and intracellular pattern recognition receptors cooperate in the recognition of Helicobacter pylori.

Rad, R; Ballhorn, W; Voland, P; Eisenächer, K; Mages, J; Rad, L; Ferstl, R; Lang, R; Wagner, H; Schmid, RM; Bauer, S; Prinz, C; Kirschning, CJ; Krug, A

doi:10.1053/j.gastro.2009.02.066

journal article

Document type:: Journal Article; Research Support, Non-U.S. Gov't
Author(s):: Rad, R; Ballhorn, W; Voland, P; Eisenächer, K; Mages, J; Rad, L; Ferstl, R; Lang, R; Wagner, H; Schmid, RM; Bauer, S; Prinz, C; Kirschning, CJ; Krug, A
Title:: Extracellular and intracellular pattern recognition receptors cooperate in the recognition of Helicobacter pylori.
Abstract:: 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.
Journal title abbreviation:: Gastroenterology
Year:: 2009
Journal volume:: 136
Journal issue:: 7
Pages contribution:: 2247-57
Language:: eng
Fulltext / DOI:: doi:10.1053/j.gastro.2009.02.066
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/19272387
Print-ISSN:: 0016-5085
TUM Institution:: II. Medizinische Klinik und Poliklinik (Gastroenterologie); Institut für Medizinische Mikrobiologie, Immunologie und Hygiene
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