Systems biology approaches to toll-like receptor signaling.
Toll-like receptor (TLR) signaling pathways constitute an evolutionarily conserved host defense system that protects against a broad range of infectious agents. Modeling of TLR signaling has been carried out at several levels. Structural models of TLRs and their adaptors, which utilize a small number of structural domains to recognize a diverse range of pathogens, provide a starting point for understanding how pathogens are recognized and signaling events initiated. Various experimental and computational techniques have been used to construct models of downstream signal transduction networks from the measurements of gene expression and chromatin structure under resting and perturbed conditions along with predicted regulatory sequence motifs. Although a complete and accurate mathematical model of all TLR signaling pathways has yet to be derived, many important modules have been identified and investigated, enhancing our understanding of innate immune responses. Extensions of these models based on emerging experimental techniques are discussed.
Laboratory of Systems Immunology, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
Alexis
A
Vandenbon
Shunsuke
S
Teraguchi
Shizuo
S
Akira
Kiyoshi
K
Takeda
Daron M
DM
Standley
D020816:Amino Acid Motifs; D000818:Animals; D005786:Gene Expression Regulation; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D049490:Systems Biology; D051193:Toll-Like Receptors / Q000737:chemistry / Q000378:metabolism*
D051193:Toll-Like Receptors