Tribbles ortholog NIPI-3 and bZIP transcription factor CEBP-1 regulate a Caenorhabditis elegans intestinal immune surveillance pathway

BMC Biology

Research Article

Wilhelm Haas¹  Anthony Anselmo²  Deborah L. McEwan²  Rhonda L. Feinbaum²  Frederick M. Ausubel²  Ruslan Sadreyev³  Annie L. Conery⁴  Nicholas Stroustrup⁵ 

[1] Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA;Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA;Department of Genetics, Harvard Medical School, Boston, MA, USA;Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA;Department of Genetics, Harvard Medical School, Boston, MA, USA;Department of Pathology, Massachusetts General Hospital, Boston, MA, USA;Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA;Department of Genetics, Harvard Medical School, Boston, MA, USA;Present Address: Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA;Department of Systems Biology, Harvard Medical School, Boston, MA, USA;

关键词: Surveillance immunity;    Tribbles-like kinase;    C/EBP;    Pseudomonas aeruginosa;    Exotoxin A;    Translational inhibition;    Caenorhabditis elegans;    Innate epithelial immunity;    Lifespan machine;   

DOI  :  10.1186/s12915-016-0334-6

 received in 2016-07-06, accepted in 2016-11-15,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundMany pathogens secrete toxins that target key host processes resulting in the activation of immune pathways. The secreted Pseudomonas aeruginosa toxin Exotoxin A (ToxA) disrupts intestinal protein synthesis, which triggers the induction of a subset of P. aeruginosa-response genes in the nematode Caenorhabditis elegans.ResultsWe show here that one ToxA-induced C. elegans gene, the Tribbles pseudokinase ortholog nipi-3, is essential for host survival following exposure to P. aeruginosa or ToxA. We find that NIPI-3 mediates the post-developmental expression of intestinal immune genes and proteins and primarily functions in parallel to known immune pathways, including p38 MAPK signaling. Through mutagenesis screening, we identify mutants of the bZIP C/EBP transcription factor cebp-1 that suppress the hypersusceptibility defects of nipi-3 mutants.ConclusionsNIPI-3 is a negative regulator of CEBP-1, which in turn negatively regulates protective immune mechanisms. This pathway represents a previously unknown innate immune signaling pathway in intestinal epithelial cells that is involved in the surveillance of cellular homeostasis. Because NIPI-3 and CEBP-1 are also essential for C. elegans development, NIPI-3 is analogous to other key innate immune signaling molecules such as the Toll receptors in Drosophila that have an independent role during development.See also companion paper by Kim et al. http://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0320-z.

【 授权许可】

CC BY   
© McEwan et al. 2016