Project

Back to overview

The Drosophila gut immune response

English title The Drosophila gut immune response
Applicant Lemaitre Bruno
Number 120709
Funding scheme Project funding (Div. I-III)
Research institution Global Health Institute EPFL SV-DO
Institution of higher education EPF Lausanne - EPFL
Main discipline Genetics
Start/End 01.09.2008 - 31.08.2011
Approved amount 642'000.00
Show all

Keywords (5)

innate immunity; gut; Insects; genetic; bacteria

Lay Summary (English)

Lead
Lay summary
Host-pathogen interactions are complex relationships in which the success of each organism depends on its ability to manipulate the other. As a result, hosts have developed surveillance and defense mechanisms to detect and eradicate invading microbes. In recent years, Drosophila has emerged as a powerful model host for the study of host-pathogen interactions. The genetic demonstration that the Drosophila Toll receptor mediates immune responses to fungal infection played a pioneering role in the identification of Toll-like receptors as essential regulators of mammalian host defenses, and fundamentally changed our understanding of innate immunity. Knowledge gained from Drosophila was also critical for scientists analyzing host defense mechanisms of insect vectors that have a severe impact on human life (e.g. Anopheles, tse-tse flies). To date, most of our knowledge on the Drosophila immune response relates to humoral and cellular defense reactions that take place in the hemolymph (the insect blood) in response to microbial injection, which is probably not the most common mode of infection in this organism. Insects such as Drosophila, which live on decaying matter and feed on fermenting medium, are more frequently exposed to invading microbes through oral infection. The aim of this project is to analyze the molecular mechanisms underlying the Drosophila gut immune response. Our goals are threefold: 1) to study the mechanisms underlying bacteria sensing in the gut, 2) to determine the cross talks between D. melanogaster gut flora and the immune response, 3) to screen for Drosophila host factors that limit bacterial growth in the gut and mediate tolerance to commensals. The gut is the major site of interaction between microbes and their host and is the first route of entry of pathogens. Studies in vertebrates have demonstrated the existence of a fine homeostatic balance between the maintenance of the gut flora and the necessarily destructive response to bacterial pathogens that colonize the gut. A dysregulation of this balance has been implicated in human diseases such as Inflammatory Bowel Disease. In addition, oral infection upon ingestion is important in nature, and is the main route of entry of many human pathogens to their insect vector hosts. Our project will provide a better understanding of the gut immune response in a model insect that will impact research in the field of innate immunity in general, as well as in insect-vectored diseases.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Drosophila immunity: analysis of PGRP-SB1 expression, enzymatic activity and function.
Zaidman-Rémy Anna, Poidevin Mickael, Hervé Mireille, Welchman David P, Paredes Juan C, Fahlander Carina, Steiner Hakan, Mengin-Lecreulx Dominique, Lemaitre Bruno (2011), Drosophila immunity: analysis of PGRP-SB1 expression, enzymatic activity and function., in PloS one, 6(2), 1-11.
Genetic evidence for a protective role of the peritrophic matrix against intestinal bacterial infection in Drosophila melanogaster.
Kuraishi Takayuki, Binggeli Olivier, Opota Onya, Buchon Nicolas, Lemaitre Bruno (2011), Genetic evidence for a protective role of the peritrophic matrix against intestinal bacterial infection in Drosophila melanogaster., in Proceedings of the National Academy of Sciences of the United States of America, 108(38), 15966-71.
Monalysin, a Novel ß-Pore-Forming Toxin from the Drosophila Pathogen Pseudomonas entomophila, Contributes to Host Intestinal Damage and Lethality.
Opota Onya, Vallet-Gély Isabelle, Vincentelli Renaud, Kellenberger Christine, Iacovache Ioan, Gonzalez Manuel Rodrigo, Roussel Alain, van der Goot Françoise-Gisou, Lemaitre Bruno (2011), Monalysin, a Novel ß-Pore-Forming Toxin from the Drosophila Pathogen Pseudomonas entomophila, Contributes to Host Intestinal Damage and Lethality., in PLoS pathogens, 7(9), 1-13.
Spiroplasma and host immunity: activation of humoral immune responses increases endosymbiont load and susceptibility to certain Gram-negative bacterial pathogens in Drosophila melanogaster.
Herren Jeremy K, Lemaitre Bruno (2011), Spiroplasma and host immunity: activation of humoral immune responses increases endosymbiont load and susceptibility to certain Gram-negative bacterial pathogens in Drosophila melanogaster., in Cellular microbiology, 13(9), 1385-96.
A secondary metabolite acting as a signalling molecule controls Pseudomonas entomophila virulence.
Vallet-Gely Isabelle, Opota Onya, Boniface Audrey, Novikov Alexey, Lemaitre Bruno (2010), A secondary metabolite acting as a signalling molecule controls Pseudomonas entomophila virulence., in Cellular microbiology, 12(11), 1666-79.
Association of hemolytic activity of Pseudomonas entomophila, a versatile soil bacterium, with cyclic lipopeptide production.
Vallet-Gely Isabelle, Novikov Alexey, Augusto Luis, Liehl Peter, Bolbach Gérard, Péchy-Tarr Maria, Cosson Pierre, Keel Christoph, Caroff Martine, Lemaitre Bruno (2010), Association of hemolytic activity of Pseudomonas entomophila, a versatile soil bacterium, with cyclic lipopeptide production., in Applied and environmental microbiology, 76(3), 910-21.
Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection.
Buchon Nicolas, Broderick Nichole A, Kuraishi Takayuki, Lemaitre Bruno (2010), Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection., in BMC biology, 8(152), 1-19.
Drosophila intestinal response to bacterial infection: activation of host defense and stem cell proliferation.
Buchon Nicolas, Broderick Nichole A, Poidevin Mickael, Pradervand Sylvain, Lemaitre Bruno (2009), Drosophila intestinal response to bacterial infection: activation of host defense and stem cell proliferation., in Cell host & microbe, 5(2), 200-11.
Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila.
Buchon Nicolas, Broderick Nichole A, Chakrabarti Sveta, Lemaitre Bruno (2009), Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila., in Genes & development, 23(19), 2333-44.
Long-range activation of systemic immunity through peptidoglycan diffusion in Drosophila.
Gendrin Mathilde, Welchman David P, Poidevin Mickael, Hervé Mireille, Lemaitre Bruno (2009), Long-range activation of systemic immunity through peptidoglycan diffusion in Drosophila., in PLoS pathogens, 5(12), 1-12.

Collaboration

Group / person Country
Types of collaboration
GHI, Lausanne Switzerland (Europe)
- Publication
Centre de Génétique Moléculaire, CNRS France (Europe)
- Publication
CNRS, Marseille France (Europe)
- Publication

Awards

Title Year
Grand prix de la Fondation Bettencourt-Schueller 2010

Associated projects

Number Title Start Funding scheme
135703 The Drosophila intestinal epithelium: an immune barrier 01.04.2011 Project funding (Div. I-III)

Abstract

à compléter
-