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The Drosophila intestinal epithelium: an immune barrier

English title The Drosophila intestinal epithelium: an immune barrier
Applicant Lemaitre Bruno
Number 135703
Funding scheme Project funding
Research institution Global Health Institute EPFL SV-DO
Institution of higher education EPF Lausanne - EPFL
Main discipline Genetics
Start/End 01.04.2011 - 31.03.2013
Approved amount 445'000.00
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Keywords (4)

innate immunity; Drosophila; insect vector; gut

Lay Summary (English)

Lead
Lay summary
The gut combines and integrates very different physiological functions required for maintaining the equilibrium of the whole organism. In addition to its role in digestion, it is the main entry route for pathogens, and a reservoir for resident bacteria that must be tolerated. Finally, the intestinal epithelium undergoes a constant renewal required to maintain the integrity of this barrier. However, little is known about how these functions are regulated and coordinated, or what mechanisms are required to ensure gut homeostasis upon exposure to external challenges such as bacterial infection.
In recent years, Drosophila has emerged as a powerful model to dissect host-pathogen interactions, leading to the paradigm of antimicrobial peptide regulation by the Toll and Imd signaling pathways. The strength of this model is due to the availability of powerful and cost effective genetic and genomic tools, as well as its high degree of similarity to vertebrate innate immunity. Using an integrated approach, our goal will be to study the mechanisms that make the gut an efficient and interactive
barrier despite its constant interactions with microbes. We will also focus our attention on the regulatory mechanisms that restore normal gut function upon challenge with bacteria. This project will utilize integrated approaches to dissect not only the gut immune response, but also gut homeostasis and physiology in the presence of microbiota, as well as strategies used by entomopathogens to circumvent these defenses. We believe that the fundamental knowledge generated on Drosophila gut immunity will serve as a paradigm of epithelial immune reactivity and have broader impacts on our comprehension of animal immune defense mechanisms and gut homeostasis.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Autocrine and paracrine unpaired signaling regulate intestinal stem cell maintenance and division.
Osman Dani, Buchon Nicolas, Chakrabarti Sveta, Huang Yu-Ting, Su Wan-Chi, Poidevin Mickaël, Tsai Yu-Chen, Lemaitre Bruno (2012), Autocrine and paracrine unpaired signaling regulate intestinal stem cell maintenance and division., in Journal of cell science, 125(Pt 24), 5944-9.
Gut-associated microbes of Drosophila melanogaster
Broderick N.A., Lemaitre B (2012), Gut-associated microbes of Drosophila melanogaster, in Gut Microbes, 3:4, 1-16.
Infection-induced host translational blockage inhibits immune responses and epithelial renewal in the Drosophila gut.
Chakrabarti S, Liehl P, Buchon N, Lemaitre B (2012), Infection-induced host translational blockage inhibits immune responses and epithelial renewal in the Drosophila gut., in Cell host & microbe, 12(1), 60-70.
Taxonomic characterisation of Pseudomonas strain L48 and formal proposal of Pseudomonas entomophila sp. nov.
Mulet Magdalena, Gomila Margarita, Lemaitre Bruno, Lalucat Jorge, García-Valdés Elena (2012), Taxonomic characterisation of Pseudomonas strain L48 and formal proposal of Pseudomonas entomophila sp. nov., in Systematic and applied microbiology, 35(3), 145-9.
Tissue- and ligand-specific sensing of gram-negative infection in drosophila by PGRP-LC isoforms and PGRP-LE.
Neyen Claudine, Poidevin Mickaël, Roussel Alain, Lemaitre Bruno (2012), Tissue- and ligand-specific sensing of gram-negative infection in drosophila by PGRP-LC isoforms and PGRP-LE., in Journal of immunology (Baltimore, Md. : 1950), 189(4), 1886-97.
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 beta-Pore-Forming Toxin from the Drosophila Pathogen Pseudomonas entomophila, Contributes to Host Intestinal Damage and Lethality
Opota O, Vallet-Gely I, Vincentelli R, Kellenberger C, Iacovache I, Gonzalez MR, Roussel A, van der Goot FG, Lemaitre B (2011), Monalysin, a Novel beta-Pore-Forming Toxin from the Drosophila Pathogen Pseudomonas entomophila, Contributes to Host Intestinal Damage and Lethality, in PLOS PATHOGENS, 7(9), 1-13.
Negative regulation by amidase PGRPs shapes the Drosophila antibacterial response and protects the fly from innocuous infection.
Paredes Juan C, Welchman David P, Poidevin Mickaël, Lemaitre Bruno (2011), Negative regulation by amidase PGRPs shapes the Drosophila antibacterial response and protects the fly from innocuous infection., in Immunity, 35(5), 770-9.

Associated projects

Number Title Start Funding scheme
120709 The Drosophila gut immune response 01.09.2008 Project funding
146163 Compartmentalization of the Drosophila gut: molecular organization and impacts on digestion and mucosal immunity 01.04.2013 Project funding

Abstract

The gut combines and integrates very different physiological functions required for maintaining the equilibrium of the whole organism. In addition to its role in digestion, it is the main entry route for pathogens, and a reservoir for resident bacteria that must be tolerated. Finally, the intestinal epithelium undergoes a constant renewal required to maintain the integrity of this barrier. However, little is known about how these functions are regulated and coordinated, or what mechanisms are required to ensure gut homeostasis upon exposure to external challenges such as bacterial infection. In recent years, Drosophila has emerged as a powerful model to dissect host-pathogen interactions, leading to the paradigm of antimicrobial peptide regulation by the Toll and Imd signaling pathways. The strength of this model is due to the availability of powerful and cost effective genetic and genomic tools, as well as its high degree of similarity to vertebrate innate immunity. Using an integrated approach, our goal will be to study the mechanisms that make the gut an efficient and interactive barrier despite its constant interactions with microbes. We will also focus our attention on the regulatory mechanisms that restore normal gut function upon challenge with bacteria. This project will utilize integrated approaches to dissect not only the gut immune response, but also gut homeostasis and physiology in the presence of microbiota, as well as strategies used by entomopathogens to circumvent these defenses. We believe that the fundamental knowledge generated on Drosophila gut immunity will serve as a paradigm of epithelial immune reactivity and have broader impacts on our comprehension of animal immune defense mechanisms and gut homeostasis.
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