The Oct1 homolog Nubbin is a repressor of NF-κB-dependent immune gene expression that increases the tolerance to gut microbiotaReport as inadecuate




The Oct1 homolog Nubbin is a repressor of NF-κB-dependent immune gene expression that increases the tolerance to gut microbiota - Download this document for free, or read online. Document in PDF available to download.

BMC Biology

, 11:99

First Online: 06 September 2013Received: 14 June 2013Accepted: 30 August 2013DOI: 10.1186-1741-7007-11-99

Cite this article as: Dantoft, W., Davis, M.M., Lindvall, J.M. et al. BMC Biol 2013 11: 99. doi:10.1186-1741-7007-11-99

Abstract

BackgroundInnate immune responses are evolutionarily conserved processes that provide crucial protection against invading organisms. Gene activation by potent NF-κB transcription factors is essential both in mammals and Drosophila during infection and stress challenges. If not strictly controlled, this potent defense system can activate autoimmune and inflammatory stress reactions, with deleterious consequences for the organism. Negative regulation to prevent gene activation in healthy organisms, in the presence of the commensal gut flora, is however not well understood.

ResultsWe show that the Drosophila homolog of mammalian Oct1-POU2F1 transcription factor, called Nubbin Nub, is a repressor of NF-κB-Relish-driven antimicrobial peptide gene expression in flies. In nub mutants, which lack Nub-PD protein, excessive expression of antimicrobial peptide genes occurs in the absence of infection, leading to a significant reduction of the numbers of cultivatable gut commensal bacteria. This aberrant immune gene expression was effectively blocked by expression of Nub from a transgene. We have identified an upstream regulatory region, containing a cluster of octamer sites, which is required for repression of antimicrobial peptide gene expression in healthy flies. Chromatin immunoprecipitation experiments demonstrated that Nub binds to octamer-containing promoter fragments of several immune genes. Gene expression profiling revealed that Drosophila Nub negatively regulates many genes that are involved in immune and stress responses, while it is a positive regulator of genes involved in differentiation and metabolism.

ConclusionsThis study demonstrates that a large number of genes that are activated by NF-κB-Relish in response to infection are normally repressed by the evolutionarily conserved Oct-POU transcription factor Nub. This prevents uncontrolled gene activation and supports the existence of a normal gut flora. We suggest that Nub protein plays an ancient role, shared with mammalian Oct-POU transcription factors, to moderate responses to immune challenge, thereby increasing the tolerance to biotic stress.

KeywordsAntimicrobial peptides Drosophila Gene regulation Host-pathogen interaction Immune signaling Innate immunity NF-kappaB Oct -POU transcription factors Stress response AbbreviationsAMPAntimicrobial peptides

AttAttacin

B-galB-galactosidase

bpBase pairs

CadCaudal

CecCecropin

CFUColony-forming Units

ChIPChromatin immunoprecipitation

DifDorsal-related immunity factor

DiptDiptericin

GOGene ontology

IMDImmune Deficiency

IREInfection-induced response elements

kDAkiloDalton

NFNuclear factor

PBSPhosphate-buffered saline

PGRPPeptidoglycan recognition proteins

RNAiRNA interference

ROSReactive oxygen species

RT-qPCRquantitative reverse transcription polymerase chain reaction

UTRUntranslated region

wtwild type.

Electronic supplementary materialThe online version of this article doi:10.1186-1741-7007-11-99 contains supplementary material, which is available to authorized users.

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Author: Widad Dantoft - Monica M Davis - Jessica M Lindvall - Xiongzhuo Tang - Hanna Uvell - Anna Junell - Anne Beskow - Ylva En

Source: https://link.springer.com/







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