PMID: 14643884 The TLRs recognize molecular patterns that are characteristic of particular classes of microorganism, such as lipopolysaccharide (LPS; Gram-negative bacteria), double-stranded RNA (viruses) and mannan (fungi).

TLR-4 and TLR-2 require the co-receptor, CD14 and a secreted protein, MD-2 to transmit LPS or PGN signals.

--

--

--

--

--

--

--

--

--

--

TLR-4 and TLR-2 require the co-receptor, CD14 and a secreted protein, MD-2 to transmit LPS or PGN signals.

--

--

--

--

--

--

--

--

--

--

TLR-4 and TLR-2 require the co-receptor, CD14 and a secreted protein, MD-2 to transmit LPS or PGN signals.

--

--

--

--

--

--

--

--

--

TIRAP and MyD88 are recruited to both TLR-4 and TLR-2 by TIR domain interactions Signaling downstream from certain TLRs, such as TLR-2, appears to be completely dependent on MyD88 (Fig. 2) (Yamamoto et al., 2002).

--

IRAK is recruited by its DD (grey region)

IRAK is recruited by its DD (grey region)

TIRAP and MyD88 are recruited to both TLR-4 and TLR-2 by TIR domain interactions

IRAK associates with TRAF-6 in the cytoplasm.

IRAK associates with TRAF-6 in the cytoplasm. Subsequently, tumor-necrosis factor receptor (TNFR)-associated factor 6 (TRAF-6) is activated, triggering the NF-_B and mitogen-activated protein kinase (MAPK) pathways, which leads to secretion of pro-inflammatory cytokines (O¡ÇNeill, 2002; Takeda, Kaisho, & Akira, 2003)

TRAF-6 forms a complex with TAB1-TAB2-TAK1 upon which TAK1 mediates downstream NF-_B, p38, ERK and JNK activation.

PMID: 14643884 The TLRs recognize molecular patterns that are characteristic of particular classes of microorganism, such as lipopolysaccharide (LPS; Gram-negative bacteria), double-stranded RNA (viruses) and mannan (fungi).

TRAF-6 forms a complex with TAB1-TAB2-TAK1 upon which TAK1 mediates downstream NF-_B, p38, ERK and JNK activation.

TRAF-6 forms a complex with TAB1-TAB2-TAK1 upon which TAK1 mediates downstream NF-_B, p38, ERK and JNK activation.

TIRAP exclusively regulates phenotypic maturation of DC: increase of CD40, CD80 and CD86 surface expression. IL-12 p70 is produced only in response to TLR-4 signaling. whereas stimulation through TLR-2 with Staphylococcus aureus peptidoglycan (PGN) results only in the release of the IL-12 p40 (Fig. 2) (Re& Strominger, 2001; Nau, Schlesinger, Richmond, & Young, 2003) c-Rel and NF-_B1/p50 are essential for LPS-induced IL-12 production (Ouaaz, Arron, Zheng, Choi, & Beg, 2002)

TIRAP exclusively regulates phenotypic maturation of DC: increase of CD40, CD80 and CD86 surface expression. IL-12 p70 is produced only in response to TLR-4 signaling.

TIRAP exclusively regulates phenotypic maturation of DC: increase of CD40, CD80 and CD86 surface expression. IL-12 p70 is produced only in response to TLR-4 signaling.

PMID: 14643884, 11937546 initiated upon LPS binding to TLR-4, predominantly leading to nuclear factor NF-kB and mitogen-activated protein (MAP) kinases activation. PKC isoforms actively participate in several TLR signaling pathways. PMID: 14643884, 11521059 Nevertheless, NF-kB and MAPKs can still be activated by TLR-4 but not TLR-2 in DCs derived from MyD88 ¡Ý/¡Ý mice, supporting the existence of an alternative, MyD88-independent pathway.

PMID: 14643884 initiated upon LPS binding to TLR-4, predominantly leading to nuclear factor (NF)-kB and mitogen-activated protein (MAP) kinases activation. PKC isoforms actively participate in several TLR signaling pathways. PMID: 14643884, 11521059 Nevertheless, NF-kB and MAPKs can still be activated by TLR-4 but not TLR-2 in DCs derived from MyD88 ¡Ý/¡Ý mice, supporting the existence of an alternative, MyD88-independent pathway.

The cytoplasmic domains of the TLRs and members of the interleukin-1 receptor (IL-1R) family contain a conserved signal-transduction module¡½ the Toll-interleukin 1 receptor (TIR) domain through which TIR-containing adaptor molecules recruit the putative serine/threonine kinase, IL-1Rassociated kinase (IRAK)

For example, stimulation of DCs by Escherichia coli LPS results in the bioactive IL-12 p70 and interferon (IFN)-stimulated genes expression through TLR-4 IL-12 p70 is produced only in response to TLR-4 signaling. c-Rel and NF-_B1/p50 are essential for LPS-induced IL-12 production (Ouaaz, Arron, Zheng, Choi, & Beg, 2002)

TIRAP/MyD88-independent pathway downstream of TLR-4 activates IRF-3 through TICAM-1 which in turn induces INF-beta.

PMID: 14643884 The TLRs recognize molecular patterns that are characteristic of particular classes of microorganism, such as lipopolysaccharide (LPS; Gram-negative bacteria), double-stranded RNA (viruses) and mannan (fungi).

TIRAP/MyD88-independent pathway downstream of TLR-4 activates IRF-3 through TICAM-1 which in turn induces INF-beta. TIR-containing adaptor molecule (TICAM-1), can activate type I IFN-beta gene promoter directly through interferon response factor (IRF)-3 upon TLR-4 triggering