2005 Fiscal Year Final Research Report Summary
Signaling cascade and network regulating innate immunity
| Project/Area Number |
13143202
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | TOHOKU UNIVERCTIY |
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Principal Investigator |
KURATA Shoichiro Tohoku University, Graduate School of Pharmaceutical Sciences, Associate professor, 大学院薬学研究科, 助教授 (90221944)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHATA Naoyuki Graduate University for Advanced Studies, Vice-President, 先導科学研究科, 副学長 (30124217)
OCHIAI Masanori Hokkatido Univeisity, Institute of Lovvtempetature Science, Assistant professor, 低温科学研究所, 助手 (10241382)
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| Project Period (FY) |
2001 – 2005
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| Keywords | innate immunity / PGRP / self defense |
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| Research Abstract |
Innate immunity is an evolutionarily conserved self-defense mechanism against microbial infections. Therefore, analysis of innate immune reactions using model organisms such as Drosophila will provide insight into the prevention of human infectious diseases.
In Drosophila, the induction of antimicrobial peptides is a major immune response regulated by two distinct signaling pathways called the IMD pathway and the Toll pathway, which are similar to the tumor necrosis factor-a signaling and Toll-like receptor/interleukin-1 signaling pathways, respectively, in mammals. In contrast to mammalian Toll-like receptor, Drosophila Toll does not act as a receptor for pathogens. As a receptor for bacterial pathogens, we identified a peptidoglycan recognition protein (PGRP)-family member, PGRP-LE, which recognizes the peptidoglycan of Gram-negative bacteria (DAP-type) and activates the IMD pathway (PNAS, 2002). In addition to PGRP-LE, some PGRP-family members were found to act as invading bacterial recognition receptors guiding humoral and cellular immune reactions in the hemolymph and on the cell surface of immune-responsive cells in Drosophila. Upstream of some serine proteases, PGRP-LE is also required for activation of the prophenoloxidase (proPO) cascade, which is another major immune response in insects (EMBO J, 2004). In addition to the extracellular function in the hemolymph, PGRP-LE has an intracellular function of recognizing the DAP-type peptidoglycan in the cytoplasm (Nature Immunology, 2006). This is the first identified intracellular receptor for bacterial components in insects.
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Research Products
(28 results)
