IGLR-2, a Leucine-Rich Repeat Domain Containing Protein, Is Required for the Host Defense in Caenorhabditis elegans

Front Immunol. 2020 Nov 30:11:561337. doi: 10.3389/fimmu.2020.561337. eCollection 2020.

Abstract

Enterohemorrhagic Escherichia coli (EHEC), a human pathogen, also infects Caenorhabditis elegans. We demonstrated previously that C. elegans activates the p38 MAPK innate immune pathway to defend against EHEC infection. However, whether a C. elegans pattern recognition receptor (PRR) exists to regulate the immune pathway remains unknown. PRRs identified in other metazoans contain several conserved domains, including the leucine-rich repeat (LRR). By screening a focused RNAi library, we identified the IGLR-2, a transmembrane protein containing the LRR domain, as a potential immune regulator in C. elegans. Our data showed that iglr-2 regulates the host susceptibility to EHEC infection. Moreover, iglr-2 is required for pathogen avoidance to EHEC. The iglr-2 overexpressed strain, which was more resistant to EHEC originally, showed hypersusceptibility to EHEC upon knockdown of the p38 MAPK pathway. Together, our data suggested that iglr-2 plays an important role in C. elegans to defend EHEC by regulating pathogen-avoidance behavior and the p38 MAPK pathway.

Keywords: Caenorhabditis elegans; enterohemorrhagic Escherichia coli; iglr-2; innate immunity; p38 MAPK pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • CRISPR-Cas Systems
  • Caenorhabditis elegans / immunology*
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / immunology*
  • Enterohemorrhagic Escherichia coli / pathogenicity*
  • Escherichia coli Infections / immunology*
  • Escherichia coli Infections / microbiology
  • Gene Knockdown Techniques
  • Host Microbial Interactions / immunology*
  • Immunity, Innate
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • IGLR-2 protein, C elegans
  • Membrane Proteins
  • p38 Mitogen-Activated Protein Kinases