Peptidoglycan sensing by the receptor PGRP-LE in the Drosophila gut induces immune responses to infectious bacteria and tolerance to microbiota.
Gut epithelial cells contact both commensal and pathogenic bacteria, and proper responses to these bacteria require a balance of positive and negative regulatory signals. In the Drosophila intestine, peptidoglycan-recognition proteins (PGRPs), including PGRP-LE, play central roles in bacterial recognition and activation of immune responses, including induction of the IMD-NF-κB pathway. We show that bacteria recognition is regionalized in the Drosophila gut with various functional regions requiring different PGRPs. Specifically, peptidoglycan recognition by PGRP-LE in the gut induces NF-κB-dependent responses to infectious bacteria but also immune tolerance to microbiota through upregulation of pirk and PGRP-LB, which negatively regulate IMD pathway activation. Loss of PGRP-LE-mediated detection of bacteria in the gut results in systemic immune activation, which can be rescued by overexpressing PGRP-LB in the gut. Together these data indicate that PGRP-LE functions as a master gut bacterial sensor that induces balanced responses to infectious bacteria and tolerance to microbiota.
Institut de Biologie du Développement de Marseille-Luminy, CNRS UMR, Aix-Marseille Université, France.
Virginie
V
Bosco-Drayon
Mickael
M
Poidevin
Ivo Gomperts
IG
Boneca
Karine
K
Narbonne-Reveau
Julien
J
Royet
Bernard
B
Charroux
D000818:Animals; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D004885:Erwinia / Q000276:immunology* / Q000502:physiology; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D048191:Lactiplantibacillus plantarum / Q000276:immunology* / Q000502:physiology; D054892:Metagenome; D010457:Peptidoglycan / Q000276:immunology*
D002352:Carrier Proteins; D010457:Peptidoglycan; C118897:peptidoglycan recognition protein