Helicobacter pylori Exploits Cholesterol-Rich Microdomains for Induction of NF-κB-Dependent Responses and Peptidoglycan Delivery in Epithelial Cells

• DOI: 10.1128/iai.00439-10
• Publication Date: 2010-08-17T01:46:50Z
• Authors: Melanie L. Hutton; Maria Kaparakis-L...; Lorinda Turner; Ana Cardona; Terry Kwok; Richard L. Ferrero
• Keywords: NOD1; Proinflammatory cytokine; Lipid raft

ABSTRACT Infection with Helicobacter pylori cag pathogenicity island ( PAI)-positive strains is associated more destructive tissue damage and an increased risk of severe disease. The PAI encodes a type IV secretion system (TFSS) that delivers the bacterial effector molecules CagA peptidoglycan into host cell cytoplasm, thereby inducing responses in cells. It was previously shown interactions between CagL, present on TFSS pilus, α 5 β 1 integrin were critical for translocation induction cytoskeletal rearrangements epithelial As found cholesterol-rich microdomains (known as lipid rafts), we hypothesized these domains may also be involved proinflammatory mediated by NOD1 recognition H. peptidoglycan. Indeed, not only did methyl-β-cyclodextrin depletion cholesterol from cultured cells have significant effect levels NF-κB interleukin-8 (IL-8) induced bacteria intact P < 0.05), but it interfered TFSS-mediated delivery to Both effects could restored replenishment Furthermore, demonstrated first time involvement pylori. Taking results together, propose integrin, which at surface, required subsequent NF-κB-dependent . These data implicate novel platform TFSS-dependent products cytosolic pathogen molecules.