Nod1 responds to peptidoglycan delivered by the Helicobacter pylori cag pathogenicity island

Nat. Immunol. 5:1166-1174 ,2004

Speaker: 翁子玉                                Date: 2005/1/5 13:10~14:00

Commentator: 許博翔 醫師                       Place: 601 教室

Abstract:

H. pylori infection causes diseases in the stomach; however, the precise mechanism by this pathogen to induce proinflammatory response remains obscure. Cag pathogenicity island (cagPAI), which encodes the type IV secretion apparatus that can translocate bacterial proteins into gastric epithelial cells¹, induces NF-κB activation in host cells² and causes more severe gastric inflammation. To elucidate this issue, the authors supposed that an intracellular receptor for Gram-negative bacteria such as Nod1 might be involved in recognition of an H. pylori product that was transported from this apparatus. At first, they used dominant negative Nod1 plasmid and Nod1 siRNA to demonstrate that Nod1 was necessary for cagPAI⁺ H. pylori to induce NF-κB activities in HEK cells. Moreover, this effect was caused by GM-tripeptide of peptidoglycan, a motif recognized by Nod1. In peptidoglycan translocation studies, they showed that a functional cagPAI was required for H. pylori delivery of peptidoglycan to epithelial cells. By generating Nod1-defiecient mice, they demonstrated a function for Nod1 in host defense against cagPAI⁺ H. pylori. They described the mechanism by which an extracellular pathogen initiated innate immune signaling in epithelial cells through cagPAI-dependent presentation of peptidoglycan to intracellular Nod1. This mechanism may be also applicable to other noninvasive Gram-negative bacteria that cause severe mucosal inflammation in animal cells.

References:

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2.  Wolfgang Fischer, et al. Systemic mutagenesis of the H. pylori cagPAI : essential genes for CagA translocation in host cells and induction of IL-8 .Mol. Microbiol. 42,1337-1348 (2001).

3.  Stephen E. Girardin, et al. CARD4/NOD1 mediates NF-κB and JNK activation by invasive Shigella flexneri. EMBO Rep. 2,736-742 (2001)