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Neuronal NPR-15 modulates molecular and behavioral immune responses via the amphid sensory neuron-intestinal axis in C. elegans.

Benson Otarigho | Anna Frances Butts | Alejandro Aballay
eLife | 2024

The survival of hosts during infections relies on their ability to mount effective molecular and behavioral immune responses. Despite extensive research on these defense strategies in various species, including the model organism Caenorhabditis elegans, the neural mechanisms underlying their interaction remain poorly understood. Previous studies have highlighted the role of neural G-protein-coupled receptors (GPCRs) in regulating both immunity and pathogen avoidance, which is particularly dependent on aerotaxis. To address this knowledge gap, we conducted a screen of mutants in neuropeptide receptor family genes. We found that loss-of-function mutations in npr-15 activated immunity while suppressing pathogen avoidance behavior. Through further analysis, NPR-15 was found to regulate immunity by modulating the activity of key transcription factors, namely GATA/ELT-2 and TFEB/HLH-30. Surprisingly, the lack of pathogen avoidance of npr-15 mutant animals was not influenced by oxygen levels. Moreover, our studies revealed that the amphid sensory neuron ASJ is involved in mediating the immune and behavioral responses orchestrated by NPR-15. Additionally, NPR-15 was found to regulate avoidance behavior via the TRPM (transient receptor potential melastatin) gene, GON-2, which may sense the intestinal distension caused by bacterial colonization to elicit pathogen avoidance. Our study contributes to a broader understanding of host defense strategies and mechanisms underlining the interaction between molecular and behavioral immune responses.

Pubmed ID: 38446031

Research resources used in this publication

Antibodies used in this publication

None found

Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD010440
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI117911
  • Agency: NIH HHS, United States
    Id: AI117911
  • Agency: NIH HHS, United States
    Id: GM0709077

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This is a list of tools and resources that we have found mentioned in this publication.


DAVID (tool)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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WormBase (tool)

RRID:SCR_003098

Central data repository for nematode biology including complete genomic sequence, gene predictions and orthology assignments from range of related nematodes.Data concerning genetics, genomics and biology of C. elegans and related nematodes. Derived from initial ACeDB database of C. elegans genetic and sequence information, WormBase includes genomic, anatomical and functional information of C. elegans, other Caenorhabditis species and other nematodes. Maintains public FTP site where researchers can find many commonly requested files and datasets, WormBase software and prepackaged databases.

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STAR (tool)

RRID:SCR_004463

Software performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.

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Applied Biosystems (tool)

RRID:SCR_005039

An Antibody supplier

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PRISM (tool)

RRID:SCR_005375

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.

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Galaxy (tool)

RRID:SCR_006281

Open, web-based platform providing bioinformatics tools and services for data intensive genomic research. Platform may be used as a service or installed locally to perform, reproduce, and share complete analyses. Galaxy automatically tracks and manages data provenance and provides support for capturing the context and intent of computational methods. Galaxy Community has created Galaxy instances in many different forms and for many different applications including Galaxy servers, cloud services that support Galaxy instances, and virtual machines and containers that can be easily deployed for your own server.The Galaxy team is a part of BX at Penn State, and the Biology and Mathematics and Computer Science departments at Emory University.Training Infrastructure as a Service (TIaaS) is a service offered by some UseGalaxy servers to specifically support training use cases.

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QIAGEN (tool)

RRID:SCR_008539

A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.

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DA508 (organism)

RRID:WB-STRAIN:WBStrain00005474

Caenorhabditis elegans with name npr-1(n1353) X. from WB.

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PR674 (organism)

RRID:WB-STRAIN:WBStrain00030783

Caenorhabditis elegans with name che-1(p674) I. from WB.

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PS6025 (organism)

RRID:WB-STRAIN:WBStrain00030970

Caenorhabditis elegans with name qrIs2. from WB.

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CX14394 (organism)

RRID:WB-STRAIN:WBStrain00005331

Caenorhabditis elegans with name npr-5(ok1583) V. from WB.

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RB1405 (organism)

RRID:WB-STRAIN:WBStrain00032103

Caenorhabditis elegans with name Y59H11AL.1(ok1598) IV. from WB.

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MGH171 (organism)

RRID:WB-STRAIN:WBStrain00026494

Caenorhabditis elegans with name sid-1(qt9) V; alxIs9. from WB.

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IM222 (organism)

RRID:WB-STRAIN:WBStrain00022046

Caenorhabditis elegans with name npr-1(ur89) X. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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EJ1158 (organism)

RRID:WB-STRAIN:WBStrain00007128

Caenorhabditis elegans with name gon-2(q388) I. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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JPS582 (organism)

RRID:WB-STRAIN:WBStrain00022733

Caenorhabditis elegans with name che-6(e1126) IV; vxEx582. from WB.

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GR2245 (organism)

RRID:WB-STRAIN:WBStrain00007966

Caenorhabditis elegans with name skn-1(mg570) IV. from WB.

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TU3401 (organism)

RRID:WB-STRAIN:WBStrain00035057

Caenorhabditis elegans with name sid-1(pk3321) V; uIs69 V. from WB.

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PY7505 (organism)

RRID:WB-STRAIN:WBStrain00031144

Caenorhabditis elegans with name oyIs84. from WB.

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DA609 (organism)

RRID:WB-STRAIN:WBStrain00005493

Caenorhabditis elegans with name npr-1(ad609) X. from WB.

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JIN1375 (organism)

RRID:WB-STRAIN:WBStrain00022468

Caenorhabditis elegans with name hlh-30(tm1978) IV. from WB.

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JN1713 (organism)

RRID:WB-STRAIN:WBStrain00022700

Caenorhabditis elegans with name peIs1713. from WB.

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RB1325 (organism)

RRID:WB-STRAIN:WBStrain00032024

Caenorhabditis elegans with name C53C7.1(ok1442) X. from WB.

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VC2421 (organism)

RRID:WB-STRAIN:WBStrain00037320

Caenorhabditis elegans with name R106.2(ok3192) X. from WB.

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RB1429 (organism)

RRID:WB-STRAIN:WBStrain00032127

Caenorhabditis elegans with name T27D1.3(ok1626) III. from WB.

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EJ26 (organism)

RRID:WB-STRAIN:WBStrain00007119

Caenorhabditis elegans with name gon-2(q362) I. from WB.

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RB1289 (organism)

RRID:WB-STRAIN:WBStrain00031988

Caenorhabditis elegans with name C43C3.2(ok1388) X. from WB.

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PR680 (organism)

RRID:WB-STRAIN:WBStrain00030787

Caenorhabditis elegans with name che-1(p680) I. from WB.

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RB1429 (organism)

RRID:WB-STRAIN:WBStrain00032127

Caenorhabditis elegans with name T27D1.3(ok1626) III. from WB.

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CX4148 (organism)

RRID:WB-STRAIN:WBStrain00005261

Caenorhabditis elegans with name npr-1(ky13) X. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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RB1365 (organism)

RRID:WB-STRAIN:WBStrain00032064

Caenorhabditis elegans with name npr-16(ok1541) X. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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RB1938 (organism)

RRID:WB-STRAIN:WBStrain00032623

Caenorhabditis elegans with name Y116A8B.5(ok2541) IV. from WB.

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KU25 (organism)

RRID:WB-STRAIN:WBStrain00024040

Caenorhabditis elegans with name pmk-1(km25) IV. from WB.

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RB1405 (organism)

RRID:WB-STRAIN:WBStrain00032103

Caenorhabditis elegans with name Y59H11AL.1(ok1598) IV. from WB.

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RB1668 (organism)

RRID:WB-STRAIN:WBStrain00032361

Caenorhabditis elegans with name npr-19(ok2068) X. from WB.

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PR672 (organism)

RRID:WB-STRAIN:WBStrain00030781

Caenorhabditis elegans with name che-1(p672) I. from WB.

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VC2526 (organism)

RRID:WB-STRAIN:WBStrain00037384

Caenorhabditis elegans with name C50F7.1(ok3258) IV. from WB.

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DA609 (organism)

RRID:WB-STRAIN:WBStrain00005493

Caenorhabditis elegans with name npr-1(ad609) X. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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RB1332 (organism)

RRID:WB-STRAIN:WBStrain00032031

Caenorhabditis elegans with name trx-1(ok1449) II. from WB.

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CZ9957 (organism)

RRID:WB-STRAIN:WBStrain00005419

Caenorhabditis elegans with name gtl-2(n2618) IV. from WB.

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CF1038 (organism)

RRID:WB-STRAIN:WBStrain00004840

Caenorhabditis elegans with name daf-16(mu86)I from WB.

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LH202 (organism)

RRID:WB-STRAIN:WBStrain00024196

Caenorhabditis elegans with name gtl-2(tm1463) IV. from WB.

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KJ412 (organism)

RRID:WB-STRAIN:WBStrain00023529

Caenorhabditis elegans with name trx-1(jh127) II. from WB.

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RB1958 (organism)

RRID:WB-STRAIN:WBStrain00032642

Caenorhabditis elegans with name T07D4.1(ok2575) II. from WB.

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CX14394 (organism)

RRID:WB-STRAIN:WBStrain00005331

Caenorhabditis elegans with name npr-5(ok1583) V. from WB.

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RB1836 (organism)

RRID:WB-STRAIN:WBStrain00032527

Caenorhabditis elegans with name W05B5.2(ok2375) I. from WB.

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RB1836 (organism)

RRID:WB-STRAIN:WBStrain00032527

Caenorhabditis elegans with name W05B5.2(ok2375) I. from WB.

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JN1715 (organism)

RRID:WB-STRAIN:WBStrain00022701

Caenorhabditis elegans with name peIs1715. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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RB1632 (organism)

RRID:WB-STRAIN:WBStrain00032326

Caenorhabditis elegans with name T02E9.1(ok2008) V. from WB.

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Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

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