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Citation
Bonnay, F., Cohen-Berros, E., Hoffmann, M., Kim, S.Y., Boulianne, G.L., Hoffmann, J.A., Matt, N., Reichhart, J.M. (2013). big bang gene modulates gut immune tolerance in Drosophila.  Proc. Natl. Acad. Sci. U.S.A. 110(8): 2957--2962.
FlyBase ID
FBrf0220843
Publication Type
Research paper
Abstract

Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.

PubMed ID
PubMed Central ID
PMC3581892 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Proc. Natl. Acad. Sci. U.S.A.
    Title
    Proceedings of the National Academy of Sciences of the United States of America
    Publication Year
    1915-
    ISBN/ISSN
    0027-8424
    Data From Reference
    Aberrations (1)
    Alleles (7)
    Genes (8)
    Human Disease Models (1)
    Insertions (2)
    Transgenic Constructs (2)
    Transcripts (2)