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Caenorhabditis elegans RIG-I-like receptor DRH-1 signals via CARDs to activate antiviral immunity in intestinal cells

Lakshmi E Batachari1, Alyssa Y Dai1, Emily R Troemel1

  • 1School of Biological Sciences, Department of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093.

Proceedings of the National Academy of Sciences of the United States of America
|July 9, 2024
PubMed

Insights

Invertebrate RIG-I-like receptors (RLRs) signal similarly to mammals. DRH-1 in C. elegans uses caspase activation and recruitment domains (CARDs) to trigger antiviral immunity and thermotolerance.

Area of Science:

  • Innate immunity
  • Molecular signaling
  • Comparative immunology

Background:

  • Mammalian RIG-I-like receptors (RLRs) utilize caspase activation and recruitment domains (CARDs) for antiviral immune responses.
  • Invertebrate RLR signaling, particularly in Caenorhabditis elegans, remains poorly understood, with DRH-1 previously linked to RNA interference rather than transcriptional immunity.

Purpose of the Study:

  • To elucidate the downstream signaling mechanisms of the Caenorhabditis elegans RLR, DRH-1.
  • To investigate the role of DRH-1 in antiviral immunity and its signaling parallels with mammalian RLRs.

Main Methods:

  • Investigated DRH-1 signaling through its tandem CARDs (2CARD) in C. elegans.
  • Assessed the impact of DRH-1(2CARD) expression on immune gene expression, viral resistance, and thermotolerance.
  • Determined DRH-1's requirement in the intestine for immune gene induction.
  • Examined the subcellular localization of DRH-1 puncta relative to double-stranded RNA during viral infection.

Main Results:

  • DRH-1 signals via two tandem CARDs (DRH-1(2CARD)) to induce a transcriptional immune response in C. elegans.
  • Expression of DRH-1(2CARD) alone conferred increased viral resistance and thermotolerance.
  • DRH-1 is essential in the intestinal cells for inducing immune gene expression.
  • DRH-1 puncta colocalize with double-stranded RNA in the cytoplasm of intestinal cells upon viral infection.

Conclusions:

  • Caenorhabditis elegans DRH-1 utilizes CARDs to activate transcriptional antiviral immunity, similar to mammalian RLRs.
  • DRH-1 plays a crucial role in the intestine for antiviral defense and thermotolerance.
  • These findings reveal conserved mechanisms in RLR signaling between invertebrates and mammals.

Keywords:
C. elegansRIG-I-like receptorinnate immunityintracellular pathogen responseviral infection

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