Inhibition of the inflammatory response and induction of apoptosis

When a pathogen interacts with a mammalian cell, multiple receptors will simultaneously recognize these pathogens both through direct binding and by binding to opsonins on the microbe surface (Underhill and Ozinsky,

2002a). One of the key mediators of microbe detection is the Toll-like receptor (TLR) family, which plays an important role in signaling toward inflammation and apoptosis (Akira et al., 2001; Imler and Hoffmann, 2001). Ten mammalian TLRs now have been identified. Five of them (TLR2, TLR4, TLR5, TLR6, and TLR9) have been shown to respond to an array of different microbial components, such as lipopolysaccharide (LPS), lipopep-tides, peptidoglycans (PGNs), lipoteichoic acid (LTA), flagellin, and CpG motifs in DNA. By using a combination of different invariant TLRs, the immune system can recognize a broad spectrum of pathogens. Stimulation of TLR2 and TLR4 leads to the recruitment of the adaptor molecule MyD88 and the serine kinase IL-1-receptor-associated kinase (IRAK; see Underhill and Ozinsky, 2002b). Together with TRAF-6, this multiprotein assembly mediates the activation of (i) the IkB kinase (IKK) complex, which leads to activation of the nuclear factor kB (NF-kB), and (ii) the mitogen-activated g protein kinase (MAPK) kinase family (MKKs), which also leads to the activation of different transcription factors, such as activator protein-1 (AP-1).

YopP/J p

0 0

Post a comment