title: Extracellular and intracellular pattern recognition receptors cooperate in the recognition of Helicobacter pylori.
abstract: OBJECTIVE
  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.
authors.affiliation: II Medical Department, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Rad
authors.forename: Wibke
authors.initials: W
authors.lastname: Ballhorn
authors.forename: Petra
authors.initials: P
authors.lastname: Voland
authors.forename: Katharina
authors.initials: K
authors.lastname: Eisenächer
authors.forename: Jörg
authors.initials: J
authors.lastname: Mages
authors.forename: Lena
authors.initials: L
authors.lastname: Rad
authors.forename: Ruth
authors.initials: R
authors.lastname: Ferstl
authors.forename: Roland
authors.initials: R
authors.lastname: Lang
authors.forename: Hermann
authors.initials: H
authors.lastname: Wagner
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.forename: Stefan
authors.initials: S
authors.lastname: Bauer
authors.forename: Christian
authors.initials: C
authors.lastname: Prinz
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Kirschning
authors.forename: Anne
authors.initials: A
authors.lastname: Krug
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004269:DNA, Bacterial / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000175:diagnosis; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D012329:RNA, Bacterial / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051193:Toll-Like Receptors / Q000172:deficiency
chemical_list: D004269:DNA, Bacterial; D012329:RNA, Bacterial; D051192:Receptors, Pattern Recognition; D051193:Toll-Like Receptors