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Peptidoglycan Molecular Requirements Allowing Detection by the Drosophila Immune Deficiency Pathway

Authors
 Carolyn R. Stenbak  ;  Ji-Hwan Ryu  ;  Dominique Mengin-Lecreulx  ;  Bruno Lemaitre  ;  Won-Jae Lee  ;  Ivo G. Boneca  ;  Catherine Chaput  ;  Mireille Hervé  ;  Claudine Parquet  ;  Sebastien Pili-Floury  ;  François Leulier 
Citation
 JOURNAL OF IMMUNOLOGY, Vol.173(12) : 7339-7348, 2004 
Journal Title
 JOURNAL OF IMMUNOLOGY 
ISSN
 0022-1767 
Issue Date
2004
MeSH
Animals ; Anti-Bacterial Agents/biosynthesis ; Carbohydrate Sequence ; Carrier Proteins/chemistry ; Carrier Proteins/immunology* ; Carrier Proteins/metabolism* ; Cell Line ; Cytotoxins/immunology ; Cytotoxins/metabolism ; Diaminopimelic Acid/analogs & derivatives ; Diaminopimelic Acid/chemistry ; Diaminopimelic Acid/immunology ; Down-Regulation/immunology ; Drosophila Proteins/immunology ; Drosophila Proteins/metabolism ; Drosophila melanogaster/immunology* ; Drosophila melanogaster/metabolism ; Immunity, Innate ; Insect Proteins/biosynthesis ; Insect Proteins/genetics ; Lysine/chemistry ; Molecular Sequence Data ; Muramidase/pharmacology ; Peptidoglycan/chemistry ; Peptidoglycan/immunology* ; Peptidoglycan/metabolism ; Signal Transduction/genetics ; Signal Transduction/immunology* ; Virulence Factors, Bordetella/chemistry ; Virulence Factors, Bordetella/immunology ; Virulence Factors, Bordetella/metabolism
Abstract
Innate immune recognition of microbes is a complex process that can be influenced by both the host and the microbe. Drosophila uses two distinct immune signaling pathways, the Toll and immune deficiency (Imd) pathways, to respond to different classes of microbes. The Toll pathway is predominantly activated by Gram-positive bacteria and fungi, while the Imd pathway is primarily activated by Gram-negative bacteria. Recent work has suggested that this differential activation is achieved through peptidoglycan recognition protein (PGRP)-mediated recognition of specific forms of peptidoglycan (PG). In this study, we have further analyzed the specific PG molecular requirements for Imd activation through the pattern recognition receptor PGRP-LC in both cultured cell line and in flies. We found that two signatures of Gram-negative PG, the presence of diaminopimelic acid in the peptide bridge and a 1,6-anhydro form of N-acetylmuramic acid in the glycan chain, allow discrimination between Gram-negative and Gram-positive bacteria. Our results also point to a role for PG oligomerization in Imd activation, and we demonstrate that elements of both the sugar backbone and the peptide bridge of PG are required for optimum recognition. Altogether, these results indicate multiple requirements for efficient PG-mediated activation of the Imd pathway and demonstrate that PG is a complex immune elicitor.
Files in This Item:
T200404357.pdf Download
DOI
10.4049/​jimmunol.173.12.7339
Appears in Collections:
5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터) > 1. Journal Papers
Yonsei Authors
Ryu, Ji Hwan(유지환)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/112942
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