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A role for SKN-1/Nrf in pathogen resistance and immunosenescence in Caenorhabditis elegans.
PLoS Pathog. 2012; 8(4):e1002673.PP

Abstract

A proper immune response ensures survival in a hostile environment and promotes longevity. Recent evidence indicates that innate immunity, beyond antimicrobial effectors, also relies on host-defensive mechanisms. The Caenorhabditis elegans transcription factor SKN-1 regulates xenobiotic and oxidative stress responses and contributes to longevity, however, its role in immune defense is unknown. Here we show that SKN-1 is required for C. elegans pathogen resistance against both Gram-negative Pseudomonas aeruginosa and Gram-positive Enterococcus faecalis bacteria. Exposure to P. aeruginosa leads to SKN-1 accumulation in intestinal nuclei and transcriptional activation of two SKN-1 target genes, gcs-1 and gst-4. Both the Toll/IL-1 Receptor domain protein TIR-1 and the p38 MAPK PMK-1 are required for SKN-1 activation by PA14 exposure. We demonstrate an early onset of immunosenescence with a concomitant age-dependent decline in SKN-1-dependent target gene activation, and a requirement of SKN-1 to enhance pathogen resistance in response to longevity-promoting interventions, such as reduced insulin/IGF-like signaling and preconditioning H(2)O(2) treatment. Finally, we find that wdr-23(RNAi)-mediated constitutive SKN-1 activation results in excessive transcription of target genes, confers oxidative stress tolerance, but impairs pathogen resistance. Our findings identify SKN-1 as a novel regulator of innate immunity, suggests its involvement in immunosenescence and provide an important crosstalk between pathogenic stress signaling and the xenobiotic/oxidative stress response.

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Authors+Show Affiliations

Papp D
Department of Medical Chemistry, Semmelweis University, Budapest, Hungary.
Csermely P
No affiliation info available
Sőti C
No affiliation info available

MeSH

AgingAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsDNA-Binding ProteinsEnterococcus faecalisGene Expression RegulationImmunity, InnateOxidative StressPseudomonas aeruginosaRNA InterferenceSignal TransductionTranscription Factorsp38 Mitogen-Activated Protein Kinases

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22577361

Citation

Papp, Diána, et al. "A Role for SKN-1/Nrf in Pathogen Resistance and Immunosenescence in Caenorhabditis Elegans." PLoS Pathogens, vol. 8, no. 4, 2012, pp. e1002673.
Papp D, Csermely P, Sőti C. A role for SKN-1/Nrf in pathogen resistance and immunosenescence in Caenorhabditis elegans. PLoS Pathog. 2012;8(4):e1002673.
Papp, D., Csermely, P., & Sőti, C. (2012). A role for SKN-1/Nrf in pathogen resistance and immunosenescence in Caenorhabditis elegans. PLoS Pathogens, 8(4), e1002673. https://doi.org/10.1371/journal.ppat.1002673
Papp D, Csermely P, Sőti C. A Role for SKN-1/Nrf in Pathogen Resistance and Immunosenescence in Caenorhabditis Elegans. PLoS Pathog. 2012;8(4):e1002673. PubMed PMID: 22577361.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A role for SKN-1/Nrf in pathogen resistance and immunosenescence in Caenorhabditis elegans. AU - Papp,Diána, AU - Csermely,Péter, AU - Sőti,Csaba, Y1 - 2012/04/26/ PY - 2011/11/06/received PY - 2012/03/13/accepted PY - 2012/5/12/entrez PY - 2012/5/12/pubmed PY - 2012/9/11/medline SP - e1002673 EP - e1002673 JF - PLoS pathogens JO - PLoS Pathog VL - 8 IS - 4 N2 - A proper immune response ensures survival in a hostile environment and promotes longevity. Recent evidence indicates that innate immunity, beyond antimicrobial effectors, also relies on host-defensive mechanisms. The Caenorhabditis elegans transcription factor SKN-1 regulates xenobiotic and oxidative stress responses and contributes to longevity, however, its role in immune defense is unknown. Here we show that SKN-1 is required for C. elegans pathogen resistance against both Gram-negative Pseudomonas aeruginosa and Gram-positive Enterococcus faecalis bacteria. Exposure to P. aeruginosa leads to SKN-1 accumulation in intestinal nuclei and transcriptional activation of two SKN-1 target genes, gcs-1 and gst-4. Both the Toll/IL-1 Receptor domain protein TIR-1 and the p38 MAPK PMK-1 are required for SKN-1 activation by PA14 exposure. We demonstrate an early onset of immunosenescence with a concomitant age-dependent decline in SKN-1-dependent target gene activation, and a requirement of SKN-1 to enhance pathogen resistance in response to longevity-promoting interventions, such as reduced insulin/IGF-like signaling and preconditioning H(2)O(2) treatment. Finally, we find that wdr-23(RNAi)-mediated constitutive SKN-1 activation results in excessive transcription of target genes, confers oxidative stress tolerance, but impairs pathogen resistance. Our findings identify SKN-1 as a novel regulator of innate immunity, suggests its involvement in immunosenescence and provide an important crosstalk between pathogenic stress signaling and the xenobiotic/oxidative stress response. SN - 1553-7374 UR - https://www.unboundmedicine.com/medline/citation/22577361/A_role_for_SKN_1/Nrf_in_pathogen_resistance_and_immunosenescence_in_Caenorhabditis_elegans_ L2 - https://dx.plos.org/10.1371/journal.ppat.1002673 DB - PRIME DP - Unbound Medicine ER -