Toll pathway

Rutschmann, S., Kilinc, A., and Ferrandon, D., Cutting edge The toll pathway is required for resistance to gram-positive bacterial infections in Drosophila, J. Immunol. 168,4,1542,2002. 

Pasare, C. and Medzhitov, R. 2003. Toll pathway-dependent blockade of CD4+ CD25+ T cell-mediated suppression by dendritic cells. Science 299 1033-1036. 

Most remarkably, parts of the Toll pathway and its function in immunity are readily recognizable in plants. For instance, Arabidopsis has about 100 proteins containing domains similar to the cytosolic domains of Toll that transduce the intracellular signal. At least some of these proteins are required for resistance to tobacco mosaic virus, and an Arabidopsis protein similar in sequence to I-kB is required for resistance to downy mildew fungus. However, the Tolllike signaling in Arabidopsis appears to act through transcription factors that are unrelated to Dorsal or NF-kB. 

Zambon RA, Nandakumar M, Vakharia VN et al. the Toll pathway is important for an antiviral response in drosophila. Proc Natl Acad Sci USA 2005 102(20) 7257-7262. 

Ferrandon D., Jung A.C., Criqui M., Lemaitre B., Uttenweiler-Joseph S., Michaut L., Reichhart J., and Hoffmann J.A. 1998. A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway. EMBO J. 17 1217-1227. 

Immune Defense JAK-STAT Pathway PIAS proteins Map Kinase Cascades Toll-like Receptors Growth Factors... 

An additional pathway leading to very efficient EFN-(3 responses involves one of the Toll-like-recqDtors (TLR), TLR3 which also senses dsRNA and is mainly expressed in dendritic cells (DC) and macrophages. Signal transduction then proceeds via the adaptor molecule TICAM/TRIF associated with the TER.-domain of... 

Horng T, Barton GM. Medzhitov R TIRAP an adapter molecule in the Toll signaling pathway. Nat Immunol 2001 2 835-841. 

Yamamoto M. Sato S. Hemmi H. Hoshino K. Kaisho T, Sanjo H, Takeuchi O. Sugiyama M. Okabe M. Takeda K, Akira S Role of adaptor TRIP in the MyD88-independent toll-like receptor signaling pathway. Science 2003 301 640-643. 

Haeberle, H.A., et al., Respiratory syncytial virus-induced activation of nuclear factor-kappaB in the lung involves alveolar macrophages and toll-like receptor 4-dependent pathways, J. Infect. Dis. 186, 9, 1199, 2002. 

IL-18 also induces IL-4, IL-10 and IL-13 production, increases IgE expression on B cells and in association with IL-2, it enhances stimulus-induced IL-4 production from TH2 cells. Bone marrow-derived basophils produce IL-4 and IL-13 in response to a stimulus from IL-18 and IL-3. IL-18 in combination with IL-12 induces IFN-y from dendritic cells and bone marrow-derived macrophages. Adhesion molecules, ICAM-1 and VCAM-1, are induced by this cytokine on synovial fibroblasts and endothelial cells. It inhibits osteoclast formation via its induction of GM-CSF from T cells. The receptors ofIL-18, IL-18Ra and IL-18R(3, share their signaling mechanisms via the IL-1R family. Toll-like receptors also share the downstream signaling pathway of IL-18 and are known to regulate IL-18 expression. 

O Neill LA. 2002. Signal transduction pathways activated by the IL-1 receptor/toll-like receptor superfamily. Curr Top Microbiol Immunol. 270 47-61. 

Figure 22.3 Signaling pathways activated by CpG DNA. CpG is thought to enter the cell via a pH-dependent step that may be receptor mediated. There is a possible role for the toll like receptor 9 (TLR-9). Once inside the cell, CpG DNA appears to act, through a number of signal transduction pathways, including the generation of reactive oxygen species (ROSs), the ubiquitination and degradation of IrcB, and activation of the mitogen-activated protein kinase (MAPK) pathways, which ultimately lead to the induction of activating protein 1 (AP-1) and nuclear factor kappa B (NF-kB).

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