| First Author | Rad R | Year | 2009 |
| Journal | Gastroenterology | Volume | 136 |
| Issue | 7 | Pages | 2247-57 |
| PubMed ID | 19272387 | Mgi Jnum | J:277966 |
| Mgi Id | MGI:6275763 | Doi | 10.1053/j.gastro.2009.02.066 |
| Citation | Rad R, et al. (2009) Extracellular and intracellular pattern recognition receptors cooperate in the recognition of Helicobacter pylori. Gastroenterology 136(7):2247-57 |
| abstractText | 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. |
