TEAM
Host pathogen interaction in the Drosophila model
Group leader : J. Royet
Using the Drosophila model to dissect the molecular mechanisms by which the nervous system of eukaryotes detects the environmental bacteria and how these bacteria-neuron interactions, in turn, modify the behavior of the host.
FOR BEGINNERS

Anterior domain of a Diptericin-cherry larval midgut infected with GFP-labbeled bacteria and stained with DAPI.
Animals live in an environment populated by microorganisms, most of which are harmless. However, because some of these microbes are pathogenic and pose a threat to the integrity of the host, animals have, over times, acquired an immune system that eliminates pathogenic invaders. In addition to strategies intended to the direct eradication of the causal agent of infection, animals, including humans, adopt behaviors, grouped under the generic term of behavioral immunity, aimed at reducing the impact of infection on themselves or on their offspring. While the molecular mechanisms by which microorganisms are eliminated by the immune system are known with great precision, the mediators of behavioral immunity remain largely ignored.
We are taking advantages on the power of Drosophila genetics to dissect the molecular mechanisms by which non-immune, neuronal or glial cells detect bacteria and how this detection triggers changes in host behavior and physiology. Studies showing that mice with impaired ability to detect bacteria exhibit abnormal behavior suggest that our project will have implications beyond the Drosophila model, namely in mammals.
FOR SPECIALISTS
Since eukaryotes live in an environment heavily contaminated by microorganisms, it is not surprising that they have forged, over the times, complex and intimate relationships between them. It is also expected that eukaryotes have developed mechanisms to perceive the presence of bacteria and to adapt their immune response, their physiological status or even their comportment accordingly. Bacteria can interact with the nervous system of eukaryotes, either for the benefit of the microbe that alters the host’s comportment or to the advantages of the host that adapts its behavior to the infection. However, the molecules underlying the dialog between bacteria and neurons of their hosts are, in most cases, not identified and, when they are, their mode of action is poorly understood.
Our goal is to use the latest genetic, imaging and bio-informatics technologies to identify the players and the molecular networks that govern this peculiar prokaryotes-eukaryotes dialog. We performed our research in the genetically amenable Drosophila model whose genome is easily edited using the CRISPR/Cas9 technology and in which most fundamental biological processes are shared with mammals.
One aspect of this research deals with one specific bacteria cell wall component, called peptidoglycan (PGN). PGN is a major constituent of the bacterial call wall. When present it the host body cavity, it elicits a range of reactions in higher animals, the principal being the activation of the antibacterial immune response upon its detection by host sentinel proteins. Improper detection of microbiota-derived PGN by the NOD proteins leads to the onset of Crohn disease, one of the most prevalent inflammatory bowel diseases in humans. Previous works in the lab, has demonstrated that in infected flies, bacteria-derived PGN can be sensed by some neurons of the fly central nervous system. This PGN-neuron interaction induces a series of behavioral changes which reduce the consequences of infection on the host. We demonstrated that PGN is directly detected by very few brain octopaminergic neurons. In turn, these neurons inhibit the egg-laying behavior of infected females. We have identified proteins expressed in these neurons which enable them to sense PGN and to modulate its effects on neurons. Interestingly, these proteins that belong to the NF-ΚB pathway are the same than those required in immune cells to trigger an antibacterial response upon PGN detection. Some of these proteins are not only expressed in neurons regulating oviposition but also in external sensory neurons such as gustatory sensilla suggesting that PGN-neurons interactions also concern higher functions of the flies, such as feeding.
Hence our lab takes advantage of the power of Drosophila genetics to dissect at the molecular level, the mechanisms by which neurons are sensing PGN and how this interaction is translated into behavioral changes for the host. Recent results showing that PGN sensors and transporters are expressed in the mouse brain and that mice deficient in PGN-sensing proteins present social behavioral alterations let us believe that the mechanisms that we study could be also exist in mammals.
Selected publications
PUBLICATION
October 10th, 2020
How Bacteria Impact Host Nervous System and Behaviors: Lessons from Flies and Worms
PUBLICATION
August 24th, 2020
Gut bacteria-derived peptidoglycan induces a metabolic syndrome-like phenotype via NF-κB-dependent insulin/PI3K signaling reduction in Drosophila renal system
PUBLICATION
June 26th, 2020
Drosophila Aversive Behavior toward Erwinia carotovora carotovora Is Mediated by Bitter Neurons and Leukokinin
PUBLICATION
March 11th, 2020
Uridine Catabolism Breaks the Bonds of Commensalism
PUBLICATION
October 29th, 2019
Peptidoglycan-dependent NF-κB activation in a small subset of brain octopaminergic neurons controls female oviposition
PUBLICATION
March 14th, 2018
Lipid Catabolism Fuels Drosophila Gut Immunity
PUBLICATION
February 14th, 2018
Cytosolic and Secreted Peptidoglycan-Degrading Enzymes in Drosophila Respectively Control Local and Systemic Immune Responses to Microbiota
PUBLICATION
May 22nd, 2017
Drosophila larvae food intake cessation following exposure to Erwinia contaminated media requires odor perception, Trpa1 channel and evf virulence factor
PUBLICATION
March 7th, 2017
Peptidoglycan sensing by octopaminergic neurons modulates Drosophila oviposition.
PUBLICATION
January 13th, 2017
Inhibition of a NF-κB/Diap1 Pathway by PGRP-LF Is Required for Proper Apoptosis during Drosophila Development
PUBLICATION
October 29th, 2019
Peptidoglycan-dependent NF-κB activation in a small subset of brain octopaminergic neurons controls female oviposition
PUBLICATION
July 18th, 2017
Oligopeptide Transporters of the SLC15 Family Are Dispensable for Peptidoglycan Sensing and Transport in Drosophila.
PUBLICATION
January 8th, 2016
Bacteria sensing mechanisms in Drosophila gut: Local and systemic consequences.
PUBLICATION
January 1st, 2016
Tissue-Specific Regulation of Drosophila NF-x03BA;B Pathway Activation by Peptidoglycan Recognition Protein SC.
PUBLICATION
April 14th, 2014
Drosophila Microbiota Modulates Host Metabolic Gene Expression via IMD/NF-κB Signaling.
PUBLICATION
November 23rd, 2013
Mutations in the Drosophila ortholog of the vertebrate Golgi pH regulator (GPHR) protein disturb endoplasmic reticulum and Golgi organization and affect systemic growth.
PUBLICATION
June 4th, 2013
Mecanisms and consequences of bacteria detection by the Drosophila midgut.
PUBLICATION
December 21st, 2012
The Drosophila inner-membrane protein PMI controls cristae biogenesis and mitochondrial diameter.
PUBLICATION
August 16th, 2012
Peptidoglycan sensing by the receptor PGRP-LE in the Drosophila gut induces immune responses to infectious bacteria and tolerance to microbiota.
PUBLICATION
April 1st, 2012
SKIV2L mutations cause syndromic diarrhea, or trichohepatoenteric syndrome.
PUBLICATION
February 1st, 2012
Gut-microbiota interactions in non-mammals: what can we learn from Drosophila?
PUBLICATION
November 11th, 2011
Peptidoglycan recognition proteins: modulators of the microbiome and inflammation.
PUBLICATION
November 1st, 2011
Epithelial homeostasis and the underlying molecular mechanisms in the gut of the insect model Drosophila melanogaster.
PUBLICATION
October 1st, 2011
Toll-8/Tollo negatively regulates antimicrobial response in the Drosophila respiratory epithelium.
PUBLICATION
September 7th, 2011
Lactobacillus plantarum promotes Drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing.
PUBLICATION
April 1st, 2011
The Drosophila peptidoglycan-recognition protein LF interacts with peptidoglycan-recognition protein LC to downregulate the Imd pathway.
PUBLICATION
March 2nd, 2011
Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat.
PUBLICATION
March 1st, 2011
Inner-membrane proteins PMI/TMEM11 regulate mitochondrial morphogenesis independently of the DRP1/MFN fission/fusion pathways.
PUBLICATION
February 28th, 2011
Lack of an antibacterial response defect in Drosophila toll-9 mutant.
PUBLICATION
January 1st, 2010
Drosophila immune response: From systemic antimicrobial peptide production in fat body cells to local defense in the intestinal tract.
PUBLICATION
September 1st, 2009
Maintaining immune homeostasis in the fly gut.
PUBLICATION
June 16th, 2009
Elimination of plasmatocytes by targeted apoptosis reveals their role in multiple aspects of the Drosophila immune response.
PUBLICATION
May 1st, 2009
Bacterial detection by Drosophila peptidoglycan recognition proteins.
PUBLICATION
May 15th, 2008
The Drosophila membrane-associated protein PGRP-LF prevents IMD/JNK pathways triggering by blocking PGRP-LC activation.
PUBLICATION
May 1st, 2008
Crystal structure of Drosophila PGRP-SD suggests binding to DAP-type but not lysine-type peptidoglycan. Molecular Immunology.
PUBLICATION
April 1st, 2007
Peptidoglycan recognition proteins: pleiotropic sensors and effectors of antimicrobial defences.
PUBLICATION
February 1st, 2006
Downregulation of the Drosophila Immune Response by Peptidoglycan-Recognition Proteins SC1 and SC2.
PUBLICATION
February 1st, 2005
Sensing and signaling during infection in Drosophila.
PUBLICATION
November 1st, 2004
Infectious non-self recognition in invertebrates: lessons from Drosophila and other insect models.
PUBLICATION
November 1st, 2004
Function of the drosophila pattern-recognition receptor PGRP-SD in the detection of Gram-positive bacteria.
PUBLICATION
March 1st, 2004
Drosophila melanogaster innate immunity: an emerging role for Peptidoglycan Recognition Proteins in bacteria detection.
PUBLICATION
January 1st, 2004
Toll-dependent and Toll-independent immune responses in Drosophila.
PUBLICATION
December 19th, 2003
Dual activation of the Drosophila Toll pathway by two Pattern Recognition Receptors.
PUBLICATION
December 1st, 2003
Detection of peptidoglycans by NOD proteins.
PUBLICATION
November 15th, 2003
Silencing of Toll pathway components by direct injection of double-stranded RNA into Drosophila adult flies.
PUBLICATION
November 19th, 2002
Notch signaling controls lineage specification during Drosophila larval hematopoiesis.
PUBLICATION
April 11th, 2002
The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein.
PUBLICATION
December 13th, 2001