title: Tissue-Specific Regulation of Drosophila NF-x03BA;B Pathway Activation by Peptidoglycan Recognition Protein SC.
abstract: In Drosophila, peptidoglycan (PGN) is detected by PGN recognition proteins (PGRPs) that act as pattern recognition receptors. Some PGRPs such as PGRP-LB or PGRP-SCs are able to cleave PGN, therefore reducing the amount of immune elicitors and dampening immune deficiency (IMD) pathway activation. The precise role of PGRP-SC is less well defined because the PGRP-SC genes (PGRP-SC1a, PGRP-SC1b and PGRP-SC2) lie very close on the chromosome and have been studied using a deletion encompassing the three genes. By generating PGRP-SC-specific mutants, we reevaluated the roles of PGRP-LB, PGRP-SC1 and PGRP-SC2, respectively, during immune responses. We showed that these genes are expressed in different gut domains and that they follow distinct transcriptional regulation. Loss-of-function mutant analysis indicates that PGRP-LB is playing a major role in IMD pathway activation and bacterial load regulation in the gut, although PGRP-SCs are expressed at high levels in this organ. We also demonstrated that PGRP-SC2 is the main negative regulator of IMD pathway activation in the fat body. Accordingly, we showed that mutants for either PGRP-LB or PGRP-SC2 displayed a distinct susceptibility to bacteria depending on the infection route. Lastly, we demonstrated that PGRP-SC1 and PGRP-SC2 are required in vivo for full Toll pathway activation by Gram-positive bacteria.
authors.affiliation: Institut de Biologie du Dx00E9;veloppement de Marseille, UMR 7288, CNRS, Aix Marseille Universitx00E9;, Marseille, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Costechareyre
authors.forename: Florence
authors.initials: F
authors.lastname: Capo
authors.forename: Alexandre
authors.initials: A
authors.lastname: Fabre
authors.forename: Delphine
authors.initials: D
authors.lastname: Chaduli
authors.forename: Christine
authors.initials: C
authors.lastname: Kellenberger
authors.forename: Alain
authors.initials: A
authors.lastname: Roussel
authors.forename: Bernard
authors.initials: B
authors.lastname: Charroux
authors.forename: Julien
authors.initials: J
authors.lastname: Royet
mesh_terms: D000818:Animals; D058491:Bacterial Load / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D005216:Fat Body / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006094:Gram-Positive Bacteria / Q000276:immunology; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism*; D009928:Organ Specificity; D010457:Peptidoglycan / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D016328:NF-kappa B; D010457:Peptidoglycan; D051192:Receptors, Pattern Recognition; C118897:peptidoglycan recognition protein