Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine; Department of Molecular, Cell and Cancer Biology; Department of Neurobiology; Graduate School of Biomedical Sciences
Bacteria | Genetics and Genomics | Immunology and Infectious Disease | Microbiology
Nuclear hormone receptors (NHRs) are ligand-gated transcription factors that control adaptive host responses following recognition of specific endogenous or exogenous ligands. Although NHRs have expanded dramatically in C. elegans compared to other metazoans, the biological function of only a few of these genes has been characterized in detail. Here, we demonstrate that an NHR can activate an anti-pathogen transcriptional program. Using genetic epistasis experiments, transcriptome profiling analyses and chromatin immunoprecipitation-sequencing, we show that, in the presence of an immunostimulatory small molecule, NHR-86 binds to the promoters of immune effectors to activate their transcription. NHR-86 is not required for resistance to the bacterial pathogen Pseudomonas aeruginosa at baseline, but activation of NHR-86 by this compound drives a transcriptional program that provides protection against this pathogen. Interestingly, NHR-86 targets immune effectors whose basal regulation requires the canonical p38 MAPK PMK-1 immune pathway. However, NHR-86 functions independently of PMK-1 and modulates the transcription of these infection response genes directly. These findings characterize a new transcriptional regulator in C. elegans that can induce a protective host response towards a bacterial pathogen.
Caenorhabditis elegans, Pseudomonas aeruginosa, Immune response, Bacterial pathogens, DNA transcription, Transcriptional control, Sequence motif analysis, MAPK signaling cascades
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Copyright: © 2019 Peterson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS Genet. 2019 Jan 22;15(1):e1007935. doi: 10.1371/journal.pgen.1007935. eCollection 2019 Jan. Link to article on publisher's site
Peterson ND, Cheesman HK, P, Anderson SM, Foster KJ, Chhaya R, Perrat PN, Thekkiniath J, Yang Q, Haynes CM, Pukkila-Worley R. (2019). The nuclear hormone receptor NHR-86 controls anti-pathogen responses in C. elegans. Open Access Publications by UMMS Authors. https://doi.org/10.1371/journal.pgen.1007935. Retrieved from https://escholarship.umassmed.edu/oapubs/3716
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This work is licensed under a Creative Commons Attribution 4.0 License.