PMID: 15476921 LPS binding and signalling through TLR4 involves the LPS binding protein (LBP), CD14 and MD-2.

PMID: 15476921, 12946842 More recently, the role of innate immunity in control of this infection has been investigated with the identification of TLR2 as the PRR that detects lipophosphoglycan (LPG), a glycosylphosphatidylinositol (GPI)-anchored glycolipid, and important virulence factor, from the membrane of the parasite.

PMID: 15476921 TLR3 detects double-stranded RNA from viruses.

PMID: 15476921, 11489966 TLR5, which is the PRR that detects flagellin, is expressed only on the basolateral surface of intestinal epithelial cells thus requiring flagellin translocation or bacterial penetration of the epithelial barrier to induce stimulation.

PMID: 15476921, 10623794, 11150311, 12411706 Heat-shock proteins , a number of extracellular matrix proteins and beta-defensins have been reported to stimulate TLR4 and induce pro-inflammatory signalling.

PMID: 15476921, 10623794, 11150311, 12411706 Heat-shock proteins , a number of extracellular matrix proteins and beta-defensins have been reported to stimulate TLR4 and induce pro-inflammatory signalling.

PMID: 15476921 Upon ligand binding to the extracellular portion of these receptors, the TIR domains recruit TIR-containing adaptor molecules, including MyD88.

PMID: 15476921 This recruitment process sets up a cascade of further recruitment of adaptor molecules and activation of a number of kinases of the interleukin-1 receptor associated kinase (IRAK) family.

PMID: 15476921 Activated IRAK then recruits TRAF6 that ultimately leads to the activation of the IKK complex.

PMID: 15476921 Activated IRAK then recruits TRAF6 that ultimately leads to the activation of the IKK complex.

PMID: 15476921 The catalytic subunits of this complex phosphorylate I¦ÊBgreek small letter alpha, the inhibitory molecule that keeps NF-¦ÊappaB in an inactive state in the cytoplasm, and this then targets this molecule for ubiquitination and subsequent degradation by the proteasome.

PMID: 15476921 LPS binding and signalling through TLR4 involves the LPS binding protein (LBP), CD14 and MD-2.

PMID: 15476921 The catalytic subunits of this complex phosphorylate I¦ÊBgreek small letter alpha, the inhibitory molecule that keeps NF-¦ÊappaB in an inactive state in the cytoplasm, and this then targets this molecule for ubiquitination and subsequent degradation by the proteasome.

PMID: 15476921 The catalytic subunits of this complex phosphorylate I¦ÊBgreek small letter alpha, the inhibitory molecule that keeps NF-¦ÊappaB in an inactive state in the cytoplasm, and this then targets this molecule for ubiquitination and subsequent degradation by the proteasome.

PMID: 15476921 NF-¦ÊappaB is then free to translocate to the nucleus and drive the expression of genes, many of which are involved in the pro-inflammatory response.

PMID: 15476921, 12791997 We recently demonstrated that Nod1 senses GlcNAc-MurNAc-L-Ala-¦Ã-D-Glu-meso-DAP (GM-triDAP), a naturally occurring PGN degradation product.

PMID: 15476921, 12527755, 12514169 In contrast to Nod1, Nod2 has been implicated as a general sensor for both Gram-positive and Gram-negative bacteria since biochemical and functional analyses have identified muramyl dipeptide MurNAc-L-Ala-D-isoGln (MDP), the minimal motif in all PGNs, as the essential structure recognized by Nod2. PMID: 15476921, 12527755, 12514169 Nod2 can detect the minimal structure of PGN, which is MDP.

PMID: 15476921 Over-expression leads to auto-oligomerization of these molecules through the NBS region.

PMID: 15476921, 9575181, 9642260, 11423652 It is believed that this process potentially exposes the CARD domain that can then interact with the CARD domain of a serine/threonine kinase called RIP2 (also known and RICK or CARDIAK). PMID: 15476921 Biochemical analysis has revealed that RIP2 interacts with both Nod1 and Nod2 and mediates the activation of NF-¦ÊappaB by these molecules. PMID: 15476921, 11463746 Using an in vitro model of infection, we could show that infection of epithelial cells with S. flexneri is a physiological stimulus leading to recruitment and interaction of RIP2 with Nod1 leading to the subsequent activation of NF-B

PMID: 15476921, 10880512 This recruitment process leads to the activation of RIP2 by a mechanism referred to as ¡Èinduced proximity¡É.

PMID: 15476921, 10880512 RIP2 is likely activated following recruitment to Nod molecules allowing it to then interact with the regulatory subunit of the IKK complex, IKKgamma or NEMO.

PMID: 15476921 Again, it appears that oligomerization of IKKgamma through interactions with RIP2 induces the activation of the catalytic domains of the complex, IKKalpha and IKKbeta, leading to the phosphorylation of I¦ÊappaB-alpha, subsequent degradation of this molecule and release of NF-¦ÊappaB.

PMID: 15476921 LPS binding and signalling through TLR4 involves the LPS binding protein (LBP), CD14 and MD-2.

PMID: 15476921 Again, it appears that oligomerization of IKKgamma through interactions with RIP2 induces the activation of the catalytic domains of the complex, IKKalpha and IKKbeta, leading to the phosphorylation of I¦ÊappaB-alpha, subsequent degradation of this molecule and release of NF-¦ÊappaB.

PMID: 15476921 PTX3 participates in the complement cascade by binding to C1q and was shown to also interact with a number of microbes including A. fumigatus.

PMID: 15476921, 11894097, 11894098 RIP2-deficient mice have impaired production of IFN-gamma following stimulation of cells with IL-12.

PMID: 15476921, 11894097, 11894098 RIP2-deficient mice have impaired production of IFN-gamma following stimulation of cells with IL-12.

PMID: 15476921, 11894097, 11894098 RIP2-deficient mice have impaired production of IFN-gamma following stimulation of cells with IL-12.

PMID: 15476921 NF-B is then free to translocate to the nucleus and drive the expression of genes, many of which are involved in the pro-inflammatory response.

PMID: 15476921 LPS binding and signalling through TLR4 involves the LPS binding protein (LBP), CD14 and MD-2.

PMID: 15476921 TLR2 has been shown to recognise a number of different PAMPs, including LTA and PGN from Gram-positive bacteria, lipoproteins from Gram-negative bacteria, lipoarabinomannan from Mycobacteria spp. and zymosan, a component of the cell wall from yeast.

PMID: 15476921 TLR2 has been shown to recognise a number of different PAMPs, including LTA and PGN from Gram-positive bacteria, lipoproteins from Gram-negative bacteria, lipoarabinomannan from Mycobacteria spp. and zymosan, a component of the cell wall from yeast.

PMID: 15476921 TLR2 has been shown to recognise a number of different PAMPs, including LTA and PGN from Gram-positive bacteria, lipoproteins from Gram-negative bacteria, lipoarabinomannan from Mycobacteria spp. and zymosan, a component of the cell wall from yeast.

PMID: 15476921 TLR2 has been shown to recognise a number of different PAMPs, including LTA and PGN from Gram-positive bacteria, lipoproteins from Gram-negative bacteria, lipoarabinomannan from Mycobacteria spp. and zymosan, a component of the cell wall from yeast.

PMID: 15476921 TLR2 has been shown to recognise a number of different PAMPs, including LTA and PGN from Gram-positive bacteria, lipoproteins from Gram-negative bacteria, lipoarabinomannan from Mycobacteria spp. and zymosan, a component of the cell wall from yeast.