000181834 001__ 181834
000181834 005__ 20190416220712.0
000181834 0247_ $$2doi$$a10.4049/jimmunol.1201022
000181834 022__ $$a1550-6606
000181834 02470 $$2ISI$$a000307216000041
000181834 037__ $$aARTICLE
000181834 245__ $$aTissue- and ligand-specific sensing of gram-negative infection in drosophila by PGRP-LC isoforms and PGRP-LE
000181834 269__ $$a2012
000181834 260__ $$bAmer Assoc Immunologists$$c2012$$aBethesda
000181834 300__ $$a12
000181834 336__ $$aJournal Articles
000181834 520__ $$aThe Drosophila antimicrobial response is one of the best characterized systems of pattern recognition receptor-mediated defense in metazoans. Drosophila senses Gram-negative bacteria via two peptidoglycan recognition proteins (PGRPs), membrane-bound PGRP-LC and secreted/cytosolic PGRP-LE, which relay diaminopimelic acid (DAP)-type peptidoglycan sensing to the Imd signaling pathway. In the case of PGRP-LC, differential splicing of PGRP domain-encoding exons to a common intracellular domain-encoding exon generates three receptor isoforms, which differ in their peptidoglycan binding specificities. In this study, we used Phi31-mediated recombineering to generate fly lines expressing specific isoforms of PGRP-LC and assessed the tissue-specific roles of PGRP-LC isoforms and PGRP-LE in the antibacterial response. Our in vivo studies demonstrate the key role of PGRP-LCx in sensing DAP-type peptidoglycan-containing Gram-negative bacteria or Gram-positive bacilli during systemic infection. We also highlight the contribution of PGRP-LCa/x heterodimers to the systemic immune response to Gram-negative bacteria through sensing of tracheal cytotoxin (TCT), whereas PGRP-LCy may have a minor role in antagonizing the immune response. Our results reveal that both PGRP-LC and PGRP-LE contribute to the intestinal immune response, with a predominant role of cytosolic PGRP-LE in the midgut, the central section of endodermal origin where PGRP-LE is enriched. Our in vivo model also definitively establishes TCT as the long-distance elicitor of systemic immune responses to intestinal bacteria observed in a loss-of-tolerance model. In conclusion, our study delineates how a combination of extracellular sensing by PGRP-LC isoforms and intracellular sensing through PGRP-LE provides sophisticated mechanisms to detect and differentiate between infections by different DAP-type bacteria in Drosophila.
000181834 700__ $$0244389$$g196305$$aNeyen, Claudine
000181834 700__ $$aPoidevin, Mickaël
000181834 700__ $$aRoussel, Alain
000181834 700__ $$aLemaitre, Bruno$$0244384$$g178546
000181834 773__ $$j189$$tJournal of immunology (Baltimore, Md. : 1950)$$k4$$q1886-97
000181834 8564_ $$uhttps://infoscience.epfl.ch/record/181834/files/J%20Immunol-2012-Neyen-1886-97.pdf$$zPublisher's version$$s2406596$$yPublisher's version
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000181834 917Z8 $$x164606
000181834 917Z8 $$x182396
000181834 937__ $$aEPFL-ARTICLE-181834
000181834 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000181834 980__ $$aARTICLE