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Review
. 2001 Jan;107(1):13-9.
doi: 10.1172/JCI11837.

Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity

G Zhang  1 , S Ghosh
Affiliations
Review

Toll-like receptor-mediated NF-kappaB activation: a phylogenetically conserved paradigm in innate immunity

G Zhang et al. J Clin Invest. 2001 Jan.
No abstract available

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Figures

Figure 1
Figure 1
Sequence alignment of the intracellular signaling domains of representative members of TLR/IL-1 receptor family. Conserved residues are boxed, with identical amino acids shaded in dark gray and similar amino acids shaded in light gray. The COOH-terminal region that is indispensable for TLR- and IL-1–mediated signaling is underlined. The proline residue that is conserved among eight of the nine human TLRs, which is critical for signaling induced by TLR2 and TLR4, is marked with a triangle.
Figure 2
Figure 2
TLR-mediated signaling pathways leading to activation of NF-κB and MAPK. TLR2 is activated in response to BLPs, PGNs of Gram-positive bacteria, LAM of mycobacteria, and mannans of yeasts. TLR4 is activated by LPS of Gram-negative bacteria and LTA of Gram-negative bacteria. A secreted small molecule MD-2 is essential for TLR4 signaling. Whether bacterial products directly bind to TLRs, or whether they bind through CD14, remains to be fully established. In Drosophila, Toll is activated by Spatzle, an endogenous protein generated by a protease cascade during development and fungal infection. A different Toll-like molecule, 18-Wheeler, is activated upon bacterial infection. Whether Spatzle is also a ligand for 18-Wheeler remains to be determined. It is important to note that NF-κB and MAPK can also be activated independently of MyD88, and TLR2 can lead to apoptosis. However, the details of the pathways involved remain to be characterized.
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