Identification of a Conserved, Orphan G Protein-Coupled Receptor Required for Efficient Pathogen Clearance in Caenorhabditis elegans

Anderson, Alexandra; Chew, Yee Lian; Schafer, William R.; McMullan, Rachel

doi:10.1128/iai.00034-19

Cited by 12 publications

(15 citation statements)

References 37 publications

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“…Additionally, we found swsn-1 , part of the core SWI/SNF complex and vital for determining C. elegans lifespan, and spe-6 , which has serine/threonine kinase activity involved in spermatid differentiation 92,93 . For C. elegans the “developmental processes” GO term encompassed 186 genes and numerous pathways including muscarinic acetylcholine receptor ( egl-30, unc-17, tpa-1 ), which is an essential pathway for responding to pathogens, neuromuscular function, and is involved in antimicrobial peptide production expressed in the tail 94–96 . After the analysis of the shared GO term “developmental process,” we then looked at GO analysis of the genes enriched in S. carpocapsae young male tail.…”

Section: Resultsmentioning

confidence: 99%

Comparative Transcriptomics of heads and tails betweenSteinernema carpocapsaeandCaenorhabditis elegans

Rodriguez

Clague

McGill

et al. 2020

Preprint

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Steinernema nematodes have been widely studied for insect infection and mutualism, but little is known about the patterns of gene expression along the body of these worms or how these compare to the model organism Caenorhabditis elegans. Here we perform the first comparative analysis between the heads and tail regions of Steinernema carpocapsae and C. elegans Infective Juveniles (IJs)/dauers and young adults using single-worm RNA-seq. While we find overall agreement in gene expression there were several sets of genes with substantial differences between the two species. Gene expression in the S. carpocapsae female compared to the C. elegans hermaphrodite heads and tails revealed differences in metabolism, aging, and determination of lifespan. Young adult male heads and tails showed major differences in developmental related processes such as morphogenesis as well as neuronal development and signaling. We also found head- and tail-specific gene expression differences between S. carpocapsae IJs and C. elegans dauers for genes related to growth and development as well as neuronal signaling and activity. This study is one of the first comparative transcriptomic analyses of body parts between distantly related species of nematodes and provides insight into both the highly conserved and genetically distinctive characteristics of both species.

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Section: Resultsmentioning

confidence: 99%

Comparative Transcriptomics of heads and tails betweenSteinernema carpocapsaeandCaenorhabditis elegans

Rodriguez

Clague

McGill

et al. 2020

Preprint

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“…More recently, Anderson and colleagues found an orphan receptor PCDR-1 (pathogen clearance defective receptor-1) to be necessary for the clearance of M . nematophilum from the rectal opening [ 24 ] ( Fig 1C ). PCDR-1 is expressed in B, F, K, and U rectal cells ( Fig 1B ).…”

Section: Neuronal Gpcrs As Regulators Of Innate Immunitymentioning

confidence: 99%

Section: Neuronal Gpcrs As Regulators Of Innate Immunitymentioning

confidence: 99%

“…aeruginosa [ 26 ], while that in PCDR-1 impairs aversion to M . nematophilum [ 24 ] ( Fig 1C ). Aversion to P .…”

Section: Neuronal Gpcrs As Regulators Of Innate Immunitymentioning

confidence: 99%

“…PCDR-1 is expressed in B, F, K, and U rectal cells (Fig 1B). Its activity in these rectal epithelial cells, along with EGL-30, is critical for effective pathogen clearance in the rectum [24]. PCDR-1 also promotes aversion to M. nematophilum (Fig 1C), but the aversion phenotype does not fully account for the pathogen clearance defects in the mutant [24].…”

Section: Regulation Of Immune Response By Gpcr Signaling In the Rectal Epitheliummentioning

confidence: 99%

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G protein-coupled receptors: The choreographers of innate immunity in Caenorhabditis elegans

Venkatesh

Singh

2021

PLoS Pathog

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Caenorhabditis elegans is a free-living, bacterivorous nematode that frequently encounters pathogens while foraging for food in decomposing vegetation. Like other invertebrates, C. elegans entirely relies on its innate immune system to combat invading pathogens. A basal flight or fight response of animals is also observed in worms against infection. The former is an aversion response of C. elegans against select pathogens, and the latter is an inducible innate response comprising of pathogen-specific effectors including lysozymes, lectins, antimicrobial peptides (AMPs), and cytoprotective molecules. Although pathogen recognition in worms is poorly understood, various signaling pathways and immune effectors facilitating defense response are well studied, making this nematode an excellent model to study host-microbe interactions. In higher vertebrates such as mice and humans, sensing of infection through pathogen-associated molecular patterns (PAMPs) or host damage-associated molecular patterns (DAMPs) is primarily mediated by the toll-like receptors (TLRs), nod-like receptors (NLRs), RIG-I like receptors (RLRs), C-type lectin domain (CTLD) proteins, and AIM-like receptors (ALRs) [1]. Humans have 10 TLRs that sense PAMPs and DAMPs. However, TOL-1, the only TLR homolog in C. elegans, does not seem to be essential during infections with most pathogens, except during Salmonella enterica [2] and Serratia marcescens [3] infections. The C. elegans RIG-I like receptor DRH-1 detects products of viral replication and activates an intracellular pathogen response [4]. CLEC-39 and CLEC-49, two CTLD proteins in C. elegans, are essential for immune responses against S. marcescens and are known to bind live bacteria [5]. Despite all these findings, the molecular mechanisms involved in pattern recognition by C. elegans during a majority of infections remain elusive. In this review, we examine the roles of G protein-coupled receptors (GPCRs) as noncanonical pattern recognition receptors (PRRs) and also discuss how GPCR signaling in C. elegans regulates various immune processes.GPCRs form the largest superfamily of cell surface receptors in eukaryotes; C. elegans encodes approximately 1,300 genes encoding putative GPCRs [6]. They are involved in a variety of physiological processes [7] and also for detecting various environmental cues, including bacterial secondary metabolites [8]. In recent years, several studies on infection in C. elegans have revealed the importance of GPCRs and their signaling in host defense. In this review, we examine the role of GPCRs in innate immunity via the modulation of "flight" or "fight" responses of C. elegans. Neuronal GPCRs as regulators of innate immunityThe nervous system is the primary site of sensory perception and signal integration in animals, making it ideal for systemic regulation of immune responses. The search for PRRs and

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Similarities in the induction of the intracellular pathogen response in Caenorhabditis elegans and the type I interferon response in mammals

Lažetić,

Batachari,

Russell

et al. 2023

BioEssays

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Although the type‐I interferon (IFN‐I) response is considered vertebrate‐specific, recent findings about the Intracellular Pathogen Response (IPR) in nematode Caenorhabditis elegans indicate that there are similarities between these two transcriptional immunological programs. The IPR is induced during infection with natural intracellular fungal and viral pathogens of the intestine and promotes resistance against these pathogens. Similarly, the IFN‐I response is induced by viruses and other intracellular pathogens and promotes resistance against infection. Whether the IPR and the IFN‐I response evolved in a divergent or convergent manner is an unanswered and exciting question, which could be addressed by further studies of immunity against intracellular pathogens in C. elegans and other simple host organisms. Here we highlight similar roles played by RIG‐I‐like receptors, purine metabolism enzymes, proteotoxic stressors, and transcription factors to induce the IPR and IFN‐I response, as well as the similar consequences of these defense programs on organismal development.

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Identification of a Conserved, Orphan G Protein-Coupled Receptor Required for Efficient Pathogen Clearance in Caenorhabditis elegans

Cited by 12 publications

References 37 publications

Comparative Transcriptomics of heads and tails betweenSteinernema carpocapsaeandCaenorhabditis elegans

Comparative Transcriptomics of heads and tails betweenSteinernema carpocapsaeandCaenorhabditis elegans

G protein-coupled receptors: The choreographers of innate immunity in Caenorhabditis elegans

Similarities in the induction of the intracellular pathogen response in Caenorhabditis elegans and the type I interferon response in mammals

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