Contrasting invertebrate immune defense behaviors caused by a single gene, the Caenorhabditis elegans neuropeptide receptor gene npr-1

Rania Nakad, Basten Snoek, Wentao Yang, S. Ellendt, Franziska Schneider, T.G. Mohr, Lone Rösingh, Anna C. Masche, P.C. Rosenstiel, K. Dierking, Jan E. Kammenga, Hinrich Schulenburg

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)

Abstract

Background: The invertebrate immune system comprises physiological mechanisms, physical barriers and also behavioral responses. It is generally related to the vertebrate innate immune system and widely believed to provide
nonspecific defense against pathogens, whereby the response to different pathogen types is usually mediated by distinct signalling cascades. Recent work suggests that invertebrate immune defense can be more specific at least at
the phenotypic level. The underlying genetic mechanisms are as yet poorly understood. Results: We demonstrate in the model invertebrate Caenorhabditis elegans that a single gene, a homolog of the mammalian neuropeptide Y receptor gene, npr-1, mediates contrasting defense phenotypes towards two distinct pathogens, the Gram-positive Bacillus thuringiensis and the Gram-negative Pseudomonas aeruginosa. Our findings are based on combining quantitative trait loci (QTLs) analysis with functional genetic analysis and RNAseq-based transcriptomics. The QTL analysis focused on behavioral immune defense against B. thuringiensis, using recombinant inbred lines (RILs) and introgression lines (ILs). It revealed several defense QTLs, including one on chromosome X comprising the npr-1 gene. The wildtype N2 allele for the latter QTL was associated with reduced defense against B. thuringiensis and thus produced an opposite phenotype to that previously reported for the N2 npr-1 allele against P. aeruginosa. Analysis of npr-1 mutants confirmed these contrasting immune phenotypes for both avoidance behavior and nematode survival. Subsequent transcriptional profiling of C. elegans wildtype and npr-1 mutant suggested that npr-1 mediates defense against both pathogens through p38 MAPK signaling, insulin-like signaling, and C-type lectins. Importantly, increased defense towards P. aeruginosa seems to be additionally influenced through the induction of oxidative stress genes and activation of GATA transcription factors, while the repression of oxidative stress genes combined with activation of Ebox transcription factors appears to enhance susceptibility to B. thuringiensis. Conclusions: Our findings highlight the role of a single gene, npr-1, in fine-tuning nematode immune defense, showing the ability of the invertebrate immune system to produce highly specialized and potentially opposing immune responses via single regulatory genes.
Original languageEnglish
Article number280
Number of pages20
JournalBMC Genomics
Volume17
Issue number1
DOIs
Publication statusPublished - 1 Dec 2016

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Neuropeptide Receptors
Caenorhabditis elegans
Invertebrates
Bacillus thuringiensis
Quantitative Trait Loci
Pseudomonas aeruginosa
Immune System
Genes
Phenotype
Oxidative Stress
Alleles
GATA Transcription Factors
Neuropeptide Y Receptors
Avoidance Learning
C-Type Lectins
Architectural Accessibility
Aptitude
X Chromosome
p38 Mitogen-Activated Protein Kinases
Regulator Genes

Cite this

Nakad, Rania ; Snoek, Basten ; Yang, Wentao ; Ellendt, S. ; Schneider, Franziska ; Mohr, T.G. ; Rösingh, Lone ; Masche, Anna C. ; Rosenstiel, P.C. ; Dierking, K. ; Kammenga, Jan E. ; Schulenburg, Hinrich. / Contrasting invertebrate immune defense behaviors caused by a single gene, the Caenorhabditis elegans neuropeptide receptor gene npr-1. In: BMC Genomics. 2016 ; Vol. 17, No. 1.
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abstract = "Background: The invertebrate immune system comprises physiological mechanisms, physical barriers and also behavioral responses. It is generally related to the vertebrate innate immune system and widely believed to providenonspecific defense against pathogens, whereby the response to different pathogen types is usually mediated by distinct signalling cascades. Recent work suggests that invertebrate immune defense can be more specific at least atthe phenotypic level. The underlying genetic mechanisms are as yet poorly understood. Results: We demonstrate in the model invertebrate Caenorhabditis elegans that a single gene, a homolog of the mammalian neuropeptide Y receptor gene, npr-1, mediates contrasting defense phenotypes towards two distinct pathogens, the Gram-positive Bacillus thuringiensis and the Gram-negative Pseudomonas aeruginosa. Our findings are based on combining quantitative trait loci (QTLs) analysis with functional genetic analysis and RNAseq-based transcriptomics. The QTL analysis focused on behavioral immune defense against B. thuringiensis, using recombinant inbred lines (RILs) and introgression lines (ILs). It revealed several defense QTLs, including one on chromosome X comprising the npr-1 gene. The wildtype N2 allele for the latter QTL was associated with reduced defense against B. thuringiensis and thus produced an opposite phenotype to that previously reported for the N2 npr-1 allele against P. aeruginosa. Analysis of npr-1 mutants confirmed these contrasting immune phenotypes for both avoidance behavior and nematode survival. Subsequent transcriptional profiling of C. elegans wildtype and npr-1 mutant suggested that npr-1 mediates defense against both pathogens through p38 MAPK signaling, insulin-like signaling, and C-type lectins. Importantly, increased defense towards P. aeruginosa seems to be additionally influenced through the induction of oxidative stress genes and activation of GATA transcription factors, while the repression of oxidative stress genes combined with activation of Ebox transcription factors appears to enhance susceptibility to B. thuringiensis. Conclusions: Our findings highlight the role of a single gene, npr-1, in fine-tuning nematode immune defense, showing the ability of the invertebrate immune system to produce highly specialized and potentially opposing immune responses via single regulatory genes.",
author = "Rania Nakad and Basten Snoek and Wentao Yang and S. Ellendt and Franziska Schneider and T.G. Mohr and Lone R{\"o}singh and Masche, {Anna C.} and P.C. Rosenstiel and K. Dierking and Kammenga, {Jan E.} and Hinrich Schulenburg",
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Nakad, R, Snoek, B, Yang, W, Ellendt, S, Schneider, F, Mohr, TG, Rösingh, L, Masche, AC, Rosenstiel, PC, Dierking, K, Kammenga, JE & Schulenburg, H 2016, 'Contrasting invertebrate immune defense behaviors caused by a single gene, the Caenorhabditis elegans neuropeptide receptor gene npr-1', BMC Genomics, vol. 17, no. 1, 280. https://doi.org/10.1186/s12864-016-2603-8

Contrasting invertebrate immune defense behaviors caused by a single gene, the Caenorhabditis elegans neuropeptide receptor gene npr-1. / Nakad, Rania; Snoek, Basten; Yang, Wentao; Ellendt, S.; Schneider, Franziska; Mohr, T.G.; Rösingh, Lone; Masche, Anna C.; Rosenstiel, P.C.; Dierking, K.; Kammenga, Jan E.; Schulenburg, Hinrich.

In: BMC Genomics, Vol. 17, No. 1, 280, 01.12.2016.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Contrasting invertebrate immune defense behaviors caused by a single gene, the Caenorhabditis elegans neuropeptide receptor gene npr-1

AU - Nakad, Rania

AU - Snoek, Basten

AU - Yang, Wentao

AU - Ellendt, S.

AU - Schneider, Franziska

AU - Mohr, T.G.

AU - Rösingh, Lone

AU - Masche, Anna C.

AU - Rosenstiel, P.C.

AU - Dierking, K.

AU - Kammenga, Jan E.

AU - Schulenburg, Hinrich

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N2 - Background: The invertebrate immune system comprises physiological mechanisms, physical barriers and also behavioral responses. It is generally related to the vertebrate innate immune system and widely believed to providenonspecific defense against pathogens, whereby the response to different pathogen types is usually mediated by distinct signalling cascades. Recent work suggests that invertebrate immune defense can be more specific at least atthe phenotypic level. The underlying genetic mechanisms are as yet poorly understood. Results: We demonstrate in the model invertebrate Caenorhabditis elegans that a single gene, a homolog of the mammalian neuropeptide Y receptor gene, npr-1, mediates contrasting defense phenotypes towards two distinct pathogens, the Gram-positive Bacillus thuringiensis and the Gram-negative Pseudomonas aeruginosa. Our findings are based on combining quantitative trait loci (QTLs) analysis with functional genetic analysis and RNAseq-based transcriptomics. The QTL analysis focused on behavioral immune defense against B. thuringiensis, using recombinant inbred lines (RILs) and introgression lines (ILs). It revealed several defense QTLs, including one on chromosome X comprising the npr-1 gene. The wildtype N2 allele for the latter QTL was associated with reduced defense against B. thuringiensis and thus produced an opposite phenotype to that previously reported for the N2 npr-1 allele against P. aeruginosa. Analysis of npr-1 mutants confirmed these contrasting immune phenotypes for both avoidance behavior and nematode survival. Subsequent transcriptional profiling of C. elegans wildtype and npr-1 mutant suggested that npr-1 mediates defense against both pathogens through p38 MAPK signaling, insulin-like signaling, and C-type lectins. Importantly, increased defense towards P. aeruginosa seems to be additionally influenced through the induction of oxidative stress genes and activation of GATA transcription factors, while the repression of oxidative stress genes combined with activation of Ebox transcription factors appears to enhance susceptibility to B. thuringiensis. Conclusions: Our findings highlight the role of a single gene, npr-1, in fine-tuning nematode immune defense, showing the ability of the invertebrate immune system to produce highly specialized and potentially opposing immune responses via single regulatory genes.

AB - Background: The invertebrate immune system comprises physiological mechanisms, physical barriers and also behavioral responses. It is generally related to the vertebrate innate immune system and widely believed to providenonspecific defense against pathogens, whereby the response to different pathogen types is usually mediated by distinct signalling cascades. Recent work suggests that invertebrate immune defense can be more specific at least atthe phenotypic level. The underlying genetic mechanisms are as yet poorly understood. Results: We demonstrate in the model invertebrate Caenorhabditis elegans that a single gene, a homolog of the mammalian neuropeptide Y receptor gene, npr-1, mediates contrasting defense phenotypes towards two distinct pathogens, the Gram-positive Bacillus thuringiensis and the Gram-negative Pseudomonas aeruginosa. Our findings are based on combining quantitative trait loci (QTLs) analysis with functional genetic analysis and RNAseq-based transcriptomics. The QTL analysis focused on behavioral immune defense against B. thuringiensis, using recombinant inbred lines (RILs) and introgression lines (ILs). It revealed several defense QTLs, including one on chromosome X comprising the npr-1 gene. The wildtype N2 allele for the latter QTL was associated with reduced defense against B. thuringiensis and thus produced an opposite phenotype to that previously reported for the N2 npr-1 allele against P. aeruginosa. Analysis of npr-1 mutants confirmed these contrasting immune phenotypes for both avoidance behavior and nematode survival. Subsequent transcriptional profiling of C. elegans wildtype and npr-1 mutant suggested that npr-1 mediates defense against both pathogens through p38 MAPK signaling, insulin-like signaling, and C-type lectins. Importantly, increased defense towards P. aeruginosa seems to be additionally influenced through the induction of oxidative stress genes and activation of GATA transcription factors, while the repression of oxidative stress genes combined with activation of Ebox transcription factors appears to enhance susceptibility to B. thuringiensis. Conclusions: Our findings highlight the role of a single gene, npr-1, in fine-tuning nematode immune defense, showing the ability of the invertebrate immune system to produce highly specialized and potentially opposing immune responses via single regulatory genes.

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DO - 10.1186/s12864-016-2603-8

M3 - Article

VL - 17

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

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