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

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

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Title: Tribbles ortholog NIPI-3 and bZIP transcription factor CEBP-1 regulate a Caenorhabditis elegans intestinal immune surveillance pathway
Author: McEwan, Deborah L.; Feinbaum, Rhonda L.; Stroustrup, Nicholas; Haas, Wilhelm; Conery, Annie L.; Anselmo, Anthony; Sadreyev, Ruslan; Ausubel, Frederick M.

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Citation: McEwan, Deborah L., Rhonda L. Feinbaum, Nicholas Stroustrup, Wilhelm Haas, Annie L. Conery, Anthony Anselmo, Ruslan Sadreyev, and Frederick M. Ausubel. 2016. “Tribbles ortholog NIPI-3 and bZIP transcription factor CEBP-1 regulate a Caenorhabditis elegans intestinal immune surveillance pathway.” BMC Biology 14 (1): 105. doi:10.1186/s12915-016-0334-6. http://dx.doi.org/10.1186/s12915-016-0334-6.
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Abstract: Background: Many 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. Results: We 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. Conclusions: NIPI-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. Electronic supplementary material The online version of this article (doi:10.1186/s12915-016-0334-6) contains supplementary material, which is available to authorized users.
Published Version: doi:10.1186/s12915-016-0334-6
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5143455/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29739052
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