UMMS Affiliation

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

Publication Date

2019-01-22

Document Type

Article

Disciplines

Bacteria | Genetics and Genomics | Immunology and Infectious Disease | Microbiology

Abstract

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.

Keywords

Caenorhabditis elegans, Pseudomonas aeruginosa, Immune response, Bacterial pathogens, DNA transcription, Transcriptional control, Sequence motif analysis, MAPK signaling cascades

Rights and Permissions

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

10.1371/journal.pgen.1007935

Source

PLoS Genet. 2019 Jan 22;15(1):e1007935. doi: 10.1371/journal.pgen.1007935. eCollection 2019 Jan. Link to article on publisher's site

Journal/Book/Conference Title

PLoS genetics

Related Resources

Link to Article in PubMed

PubMed ID

30668573

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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