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Gastroenterology. 2009 Jun;136(7):2247-57. doi: 10.1053/j.gastro.2009.02.066. Epub 2009 Mar 6.

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

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  • 1II Medical Department, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany.

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.

PMID:
19272387
[PubMed - indexed for MEDLINE]
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