| Citation | McEwan DL, Feinbaum RL, Stroustrup N, Haas W, Conery AL, Anselmo A, Sadreyev R, Ausubel FM. Tribbles ortholog NIPI-3 and bZIP transcription factor CEBP-1 regulate a Caenorhabditis elegans intestinal immune surveillance pathway. BMC Biol, 2016. |
| PubMed ID | 27927200 |
| Short Description | Tribbles ortholog NIPI-3 and bZIP transcription factor CEBP-1 regulate a Caenorhabditis elegans intestinal immune surveillance pathway. GEO Record: GSE87052 Platform: GPL200 Download gene-centric, log2 transformed data: WBPaper00050515.ce.mr.csv |
| # of Conditions | 9 |
Full Description
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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. Experimental Details: WBPaper00050515:N2_rep1_2176A WBPaper00050515:N2_rep2_2176B WBPaper00050515:N2_rep3_2176C WBPaper00050515:nipi-3(fr4)_rep1_2176D WBPaper00050515:nipi-3(fr4)_rep2_2176E WBPaper00050515:nipi-3(fr4)_rep3_2176F WBPaper00050515:pmk-1(km25)_rep1_2176G WBPaper00050515:pmk-1(km25)_rep2_2176H WBPaper00050515:pmk-1(km25)_rep3_2176I. |
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