RRC ID 21913
著者 Bonnay F, Cohen-Berros E, Hoffmann M, Kim SY, Boulianne GL, Hoffmann JA, Matt N, Reichhart JM.
タイトル big bang gene modulates gut immune tolerance in Drosophila.
ジャーナル Proc Natl Acad Sci U S A
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.
巻・号 110(8)
ページ 2957-62
公開日 2013-2-19
DOI 10.1073/pnas.1221910110
PII 1221910110
PMID 23378635
PMC PMC3581892
MeSH Animals Drosophila / immunology* Drosophila Proteins / genetics* Immune Tolerance / genetics* Longevity Membrane Proteins / genetics*
IF 9.412
引用数 42
WOS 分野 IMMUNOLOGY
リソース情報
ショウジョウバエ DGRC#113094 (NP3084)