Toll-like receptor


Toll-like receptor control of the adaptive immune responses
Nature Immunology 5, 987 - 995 (2004)

”LPS、IFN-γ、酸化LDL→外因性リガンド - TLR4”ってことで、各種感染症(肺炎球菌、肺結核、ナイセリア・・・)や動脈硬化など幅広い関連が今世紀になって検討されている。感染症においては、LPSによるTLR認識が”central regulator of effective host immunity to bacterial pathogens”と考えられ、また、TLR-2はグラム陽性菌細胞壁のリポタイコ酸やペプチドグリカンを認識、TLR5は細菌鞭毛蛋白フラジェリン認識、細菌DNAやウィルスDNAもリガンドとして作用、真菌・原虫の構成成分も認識することが報告されている。RSVではTLR4が融合蛋白の認識に関わり、合成dsRNAとTLR3との関連、TLR9やTLR7などもウィルスの認識に関わる(ウィルス vol. 54 (2) 145-152, 2004

Toll-like receptors (TLRs) recognize distinct pathogen-associated molecular patterns and play a critical role in innate immune responses. They participate in the first line of defense against invading pathogens and play a significant role in inflammation, immune cell regulation, survival and proliferation. To date 11 members of the TLR family have been identified, of which TLR1, 2, 4, 5 and 6 are located on the cell surface and TLR3, 7, 8 and 9 are localized to the endosomal/lysosomal compartment. The activation of the TLR signaling pathway originates from the cytoplasmic Toll/IL-1 receptor (TIR) domain that associates with a TIR domain-containing adaptor, MyD88. Upon stimulation with ligands, MyD88 recruits IL-1 receptor-associated kinase (IRAK) to TLRs through interaction of the death domains of both molecules. IRAK activated by phosphorylation then associates with TRAF6, finally leading to activation of JNK and NF-κB. Tollip and IRAK-M interact with IRAK-1 and negatively regulate the TLR-mediated signaling pathways. MyD88-independent pathways induce activation of IRF3 and expression of interferon-β. TIR-domain containing adaptors such as TIRAP, TRIF and TRAM regulate TLR-mediated signaling pathways by providing specificity for individual TLR signaling cascades.


Molecular surface of toll-like receptor


Toll-Like Receptor 2 Deficiency Delays Pneumococcal Phagocytosis and Impairs Oxidative Killing by Granulocytes
Infection and Immunity, December 2005, p. 8397-8401, Vol. 73, No. 12

the model involves mitogen-activated protein kinases, phosphatidylinositol 3-kinase/Akt signaling, and the TLR3-associated adaptor molecule TRIF but not MyD88-dependent activation of the transcription factors NF-{kappa}B or interferon regulatory factor/interferon-sensitive response-element pathways.
Involvement of Toll-like Receptor 3 in the Immune Response of Lung Epithelial Cells to Double-stranded RNA and Influenza A Virus
J. Biol. Chem., Vol. 280, Issue 7, 5571-5580, February 18, 2005
its evasion by viruses and a potential role in crosspriming is addressed, which reveals a clearer appreciation of the contribution of TLR3 to antiviral immunity.
TLR3 in antiviral immunity: key player or bystander?
Trends in Immunology Volume 26, Issue 9, September 2005, Pages 462-468

Review:The toll of Toll-like receptors, especially toll-like receptor 2, on murine atherosclerosis.
Curr Drug Targets. 2007 Dec;8(12):1230-8.

Toll-like receptors (TLRs) – which sense microbial pathogens and initiate immediate inflammatory responses – are potentially involved in the pathogenesis of atherosclerosis.
Toll-like receptors and atherosclerosis: oxidized LDL as an endogenous Toll-like receptor ligand
Future Cardiology, Volume 1, Number 6, November 2005 , pp. 785-792(8)

by internalmedicine | 2009-02-08 08:44 | 医学  

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