ArticleProceedings of the National Academy of Sciences of the United States of America2013
big bang gene modulates gut immune tolerance in Drosophila.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 77 citations in OpenAlex.
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- Intestinal Immune Deficiency and Juvenile Hormone Signaling Mediate a Metabolic Trade-off in AdultMetabolites · 2023Article
- Effect ofAntioxidants (Basel, Switzerland) · 2023Article
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- The Intestinal Immune Defense System in Insects.International journal of molecular sciences · 2022Review
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- The Role of Microbiota inFrontiers in aging · 2022Review
- Molecular basis for epithelial morphogenesis and ion transport in the Malpighian tubule.Current opinion in insect science · 2021Review
- A Non-stop identity complex (NIC) supervises enterocyte identity and protects from premature aging.eLife · 2021Article
- Comparative Transcriptomic Analyses of Antibiotic-Treated and Normally RearedFrontiers in cell and developmental biology · 2021Article
- Ageing, metabolism and the intestine.EMBO reports · 2020Review
- TheFrontiers in microbiology · 2020Article
- Convergence of longevity and immunity: lessons from animal models.Biogerontology · 2019Review
- Anatomy and Physiology of the Digestive Tract ofGenetics · 2018Review
- The apical scaffold big bang binds to spectrins and regulates the growth ofThe Journal of cell biology · 2018Article
- Article
- The interplay between immunity and aging inF1000Research · 2018Review
- Interaction Between Familial Transmission and a Constitutively Active Immune System Shapes Gut Microbiota inGenetics · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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