Innate Immunity in C. elegans

Engelmann, Ilka; Pujol, Nathalie

doi:10.1007/978-1-4419-8059-5_6

Cited by 101 publications

(97 citation statements)

References 89 publications

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“…C. elegans is a useful model to study infectious disease. A rich body of literature demonstrates that molecular mechanisms of infectious disease progression in C. elegans are mechanistically similar to humans ( Pukkila-Worley et al 2009, 2011; also reviewed in Engelmann and Pujol 2010;Marsh and May 2012). We identified seven mutants, CMP1, IFF11, SAP8, DOT4, ZCF15, orf19.1219, and orf19.6713, representing 10% of the mutants screened, that were unable to illicit the Dar response, previously described as a robust disease phenotypes in C. elegans ( Figure S4A), in particular, a deformity in the post anal region (Dar) (Jain et al 2009).…”

Section: Resultsmentioning

confidence: 99%

Zinc Cluster Transcription Factors Alter Virulence in Candida albicans

et al. 2017

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Almost all humans are colonized with Candida albicans. However, in immunocompromised individuals, this benign commensal organism becomes a serious, life-threatening pathogen. Here, we describe and analyze the regulatory networks that modulate innate responses in the host niches. We identified Zcf15 and Zcf29, two Zinc Cluster transcription Factors (ZCF) that are required for C. albicans virulence. Previous sequence analysis of clinical C. albicans isolates from immunocompromised patients indicates that both ZCF genes diverged during clonal evolution. Using in vivo animal models, ex vivo cell culture methods, and in vitro sensitivity assays, we demonstrate that knockout mutants of both ZCF15 and ZCF29 are hypersensitive to reactive oxygen species (ROS), suggesting they help neutralize the host-derived ROS produced by phagocytes, as well as establish a sustained infection in vivo. Transcriptomic analysis of mutants under resting conditions where cells were not experiencing oxidative stress revealed a large network that control macro and micronutrient homeostasis, which likely contributes to overall pathogen fitness in host niches. Under oxidative stress, both transcription factors regulate a separate set of genes involved in detoxification of ROS and down-regulating ribosome biogenesis. ChIP-seq analysis, which reveals vastly different binding partners for each transcription factor (TF) before and after oxidative stress, further confirms these results. Furthermore, the absence of a dominant binding motif likely facilitates their mobility, and supports the notion that they represent a recent expansion of the ZCF family in the pathogenic Candida species. Our analyses provide a framework for understanding new aspects of the interface between C. albicans and host defense response, and extends our understanding of how complex cell behaviors are linked to the evolution of TFs.

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Section: Resultsmentioning

confidence: 99%

Zinc Cluster Transcription Factors Alter Virulence in Candida albicans

et al. 2017

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“…Microbacterium nematophilum, Leucobacter sp., Enterococcus faecalis, Staphylococcus aureus and Bacillus thuringiensis), fungi (e.g. Drechmeria coniospora, Nematocida parisii, Candida albicans) and also a nodavirus (Orsay virus) [6]. Some of the used pathogens interact with C. elegans in nature, especially the microsporidian N. parisii [7], Orsay virus [8], P. aeruginosa [9], Leucobacter sp.…”

Section: Brief Overview Of the Caenorhabditis Elegans Immune Systemmentioning

confidence: 99%

Antimicrobial effectors in the nematode Caenorhabditis elegans : an outgroup to the Arthropoda

Dierking

Yang

Schulenburg

2016

Phil. Trans. R. Soc. B

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One contribution of 13 to a theme issue 'Evolutionary ecology of arthropod antimicrobial peptides'. Nematodes and arthropods likely form the taxon Ecdysozoa. Information on antimicrobial effectors from the model nematode Caenorhabditis elegans may thus shed light on the evolutionary origin of these defences in arthropods. This nematode species possesses an extensive armory of putative antimicrobial effector proteins, such as lysozymes, caenopores (or saposin-like proteins), defensin-like peptides, caenacins and neuropeptide-like proteins, in addition to the production of reactive oxygen species and autophagy. As C. elegans is a bacterivore that lives in microbe-rich environments, some of its effector peptides and proteins likely function in both digestion of bacterial food and pathogen elimination. In this review, we provide an overview of C. elegans immune effector proteins and mechanisms. We summarize the experimental evidence of their antimicrobial function and involvement in the response to pathogen infection. We further evaluate the microbe-induced expression of effector genes using WormExp, a recently established database for C. elegans gene expression analysis. We emphasize the need for further analysis at the protein level to demonstrate an antimicrobial activity of these molecules both in vitro and in vivo.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.

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“…While C. elegans lacks an adaptive immune response, it has a robust innate immune response, and has become an established model for innate immunity studies (Engelmann and Pujol 2010;Irazoqui and Ausubel 2010;Pukkila-Worley and Ausubel 2012). In response to infection, C. elegans produces numerous antimicrobial proteins including lysozymes, saposin-domain-containing proteins, defensin-like molecules, and many others (Ewbank 2006;Ewbank and Zugasti 2011).…”

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confidence: 99%

Comparative Genomics RNAi Screen Identifies Eftud2 as a Novel Regulator of Innate Immunity

et al. 2014

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The extent of the innate immune response is regulated by many positively and negatively acting signaling proteins. This allows for proper activation of innate immunity to fight infection while ensuring that the response is limited to prevent unwanted complications. Thus mutations in innate immune regulators can lead to immune dysfunction or to inflammatory diseases such as arthritis or atherosclerosis. To identify novel innate immune regulators that could affect infectious or inflammatory disease, we have taken a comparative genomics RNAi screening approach in which we inhibit orthologous genes in the nematode Caenorhabditis elegans and murine macrophages, expecting that genes with evolutionarily conserved function also will regulate innate immunity in humans. Here we report the results of an RNAi screen of approximately half of the C. elegans genome, which led to the identification of many candidate genes that regulate innate immunity in C. elegans and mouse macrophages. One of these novel conserved regulators of innate immunity is the mRNA splicing regulator Eftud2, which we show controls the alternate splicing of the MyD88 innate immunity signaling adaptor to modulate the extent of the innate immune response.

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Innate Immunity in C. elegans

Cited by 101 publications

References 89 publications

Zinc Cluster Transcription Factors Alter Virulence in Candida albicans

Zinc Cluster Transcription Factors Alter Virulence in Candida albicans

Antimicrobial effectors in the nematode Caenorhabditis elegans : an outgroup to the Arthropoda

Comparative Genomics RNAi Screen Identifies Eftud2 as a Novel Regulator of Innate Immunity

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