Cytosolic and Secreted Peptidoglycan-Degrading Enzymes in Drosophila Respectively Control Local and Systemic Immune Responses to Microbiota

Publication date: 14 February 2018
Source:Cell Host & Microbe, Volume 23, Issue 2
Author(s): Bernard Charroux, Florence Capo, C. Léopold Kurz, Sabine Peslier, Delphine Chaduli, Annelise Viallat-lieutaud, Julien Royet
Gut-associated bacteria produce metabolites that both have a local influence on the intestinal tract and act at a distance on remote organs. In Drosophila, bacteria-derived peptidoglycan (PGN) displays such a dual role. PGN triggers local antimicrobial peptide production by enterocytes; it also activates systemic immune responses in fat-body cells and modulates fly behavior by acting on neurons. How these responses to a single microbiota-derived compound are simultaneously coordinated is not understood. We show here that the PGRP-LB locus generates both cytosolic and secreted PGN-cleaving enzymes. Through genetic analysis, we demonstrate that the cytosolic PGRP-LB isoforms cell-autonomously control the intensity of NF-κB activation in enterocytes, whereas the secreted isoform prevents massive and detrimental gut-derived PGN dissemination throughout the organism. This study explains how Drosophila are able to uncouple the modulation of local versus systemic responses to a single gut-bacteria-derived product by using isoform-specific enzymes.

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Teaser

Since microbiota-derived peptidoglycan activates NF-κB signaling in the gut and remote organs, its levels need to be controlled in vivo. Charroux et al. show how, by generating both secreted and cytosolic peptidoglycan-cleaving enzymes, Drosophila uncouple the modulation of local versus systemic responses to a single gut-bacteria-derived product.


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