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Gut immunity is regulated by intricate and dynamic mechanisms to ensure homeostasis despite a constantly changing microbial environment. Several regulatory factors have been described to participate in feedback responses to prevent aberrant immune activity. Little is, however, known about how transcriptional programs are directly tuned to efficiently adapt host gut tissues to the current microbiome. Here we show that the POU/Oct gene nubbin (nub) encodes two transcription factor isoforms, Nub-PB and Nub-PD, which antagonistically regulate immune gene expression in Drosophila. Global transcriptional profiling of adult flies overexpressing Nub-PB in immunocompetent tissues revealed that this form is a strong transcriptional activator of a large set of immune genes. Further genetic analyses showed that Nub-PB is sufficient to drive expression both independently and in conjunction with nuclear factor kappa B (NF-κB), JNK and JAK/STAT pathways. Similar overexpression of Nub-PD did, conversely, repress expression of the same targets. Strikingly, isoform co-overexpression normalized immune gene transcription, suggesting antagonistic activities. RNAi-mediated knockdown of individual nub transcripts in enterocytes confirmed antagonistic regulation by the two isoforms and that both are necessary for normal immune gene transcription in the midgut. Furthermore, enterocyte-specific Nub-PB expression levels had a strong impact on gut bacterial load as well as host lifespan. Overexpression of Nub-PB enhanced bacterial clearance of ingested Erwinia carotovora carotovora 15. Nevertheless, flies quickly succumbed to the infection, suggesting a deleterious immune response. In line with this, prolonged overexpression promoted a proinflammatory signature in the gut with induction of JNK and JAK/STAT pathways, increased apoptosis and stem cell proliferation. These findings highlight a novel regulatory mechanism of host-microbe interactions mediated by antagonistic transcription factor isoforms.
Pubmed ID: 29499056 RIS Download
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View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-EGFP}5a.2 from BDSC.
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View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on April 12,2023. Matlab code for two-factor (location and year) analysis-of-variance model for the calculation of climate anomalies, in which the reference interval is specified as the full length of the dataset. This scheme avoids the affects of shorter (e.g. 1961-1990) reference intervals on the temporal evolution of the spatial standard deviation of climate anomalies. Data files provided.
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View all literature mentionsDrosophila melanogaster with name w[1118]; Rel[E20] e[s] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mW.hs]=GawB}c564 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02973}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name P{KK113120}VIE-260B from Flybase.
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View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mW.hs]=GawB}nubbin-AC-62, P{w[+mC]=UAS-mCherry.NLS}2; P{w[+mC]=UAS-Nslmb-vhhGFP4}3/TM3, Sb[1] Ser[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; Mi{y[+mDint2]=MIC}nub[MI05126] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118] from BDSC.
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