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

BMC Biology

Research Article

Ylva Engström¹  Monica M Davis¹  Xiongzhuo Tang¹  Anna Junell¹  Widad Dantoft¹  Anne Beskow²  Hanna Uvell³  Jessica M Lindvall⁴ 

[1] Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91, Stockholm, Sweden;Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91, Stockholm, Sweden;Department of Pathology and Cell Biology, Columbia University, New York, USA;Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91, Stockholm, Sweden;Laboratories for Chemical Biology Umeå (LCBU), Umeå University, SE-901 87, Umeå, Sweden;Huddinge Genomics Core Facilities, Department of Biosciences and Nutrition, Karolinska Institute, SE-141 87, Huddinge, Sweden;

关键词: Antimicrobial peptides;    Drosophila;    Gene regulation;    Host-pathogen interaction;    Immune signaling;    Innate immunity;    NF-kappaB;    Oct /POU transcription factors;    Stress response;   

DOI  :  10.1186/1741-7007-11-99

 received in 2013-06-14, accepted in 2013-08-30,  发布年份 2013

来源: Springer

【 摘 要 】

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 nub1 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.

【 授权许可】

Unknown   
© Dantoft et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.