An Intracellular Pathogen Response Pathway Promotes Proteostasis in C. elegans

Reddy, Kirthi C.; Dror, Tal; Sowa, Jessica N.; Panek, Johan; Chen, Kevin; Lim, Efrem S.; Wang, David; Troemel, Emily R.

doi:10.1016/j.cub.2017.10.009

Cited by 97 publications

(240 citation statements)

References 27 publications

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“…When infected intracellularly with virus or microsporidia, C. elegans hosts upregulate an overlapping set of loci. The resulting gene expression patterns are quite distinct from those associated with unnatural, extracellular infection (Bakowski et al, 2014a;Reddy et al, 2017). Caenorhabditis elegans encounters fungi and bacteria in the wild as well.…”

Section: Not Described Likely Facultative Bmentioning

confidence: 99%

A Model for Evolutionary Ecology of Disease: The Case for Caenorhabditis Nematodes and Their Natural Parasites

Gibson

Morran

2017

Journal of Nematology

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Many of the outstanding questions in disease ecology and evolution call for combining observation of natural hostparasite populations with experimental dissection of interactions in the field and the laboratory. The ''rewilding'' of model systems holds great promise for this endeavor. Here, we highlight the potential for development of the nematode Caenorhabditis elegans and its close relatives as a model for the study of disease ecology and evolution. This powerful laboratory model was disassociated from its natural habitat in the 1960s. Today, studies are uncovering that lost natural history, with several natural parasites described since 2008. Studies of these natural Caenorhabditis-parasite interactions can reap the benefits of the vast array of experimental and genetic tools developed for this laboratory model. In this review, we introduce the natural parasites of C. elegans characterized thus far and discuss resources available to study them, including experimental (co)evolution, cryopreservation, behavioral assays, and genomic tools. Throughout, we present avenues of research that are interesting and feasible to address with caenorhabditid nematodes and their natural parasites, ranging from the maintenance of outcrossing to the community dynamics of host-associated microbes. In combining natural relevance with the experimental power of a laboratory supermodel, these fledgling host-parasite systems can take on fundamental questions in evolutionary ecology of disease.

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Section: Not Described Likely Facultative Bmentioning

confidence: 99%

A Model for Evolutionary Ecology of Disease: The Case for Caenorhabditis Nematodes and Their Natural Parasites

Gibson

Morran

2017

Journal of Nematology

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“…Three antiviral responses are known of which RNA interference (RNAi) and uridylation both target viral RNA for degradation [7,[9][10][11]. The third response, the so-called Intracellular Pathogen Response (IPR), is thought to relieve proteotoxic stress from the infection by the OrV and other intracellular pathogens [12][13][14][15]. The 80 genes involved in the IPR pathway are controlled by pals-22 and pals-25 that function as a molecular switch between growth and antiviral defense.…”

Section: Introductionmentioning

confidence: 99%

“…The 80 genes involved in the IPR pathway are controlled by pals-22 and pals-25 that function as a molecular switch between growth and antiviral defense. The gene pals-22 promotes development and lifespan, whereas pals-25 stimulates pathogen resistance [13,14]. Of the 80 IPR genes that become differentially expressed upon infection, 25 genes belong to the pals-gene family.…”

Section: Introductionmentioning

confidence: 99%

Balancing selection of the Intracellular Pathogen Response in natural Caenorhabditis elegans populations

Sluijs

Bosman

Pankok

et al. 2019

Preprint

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23 0031317482998 24 Mark.Sterken@wur.nl 25 Our work provides evidence that balancing genetic selection shapes the transcriptional defence against pathogens 48 in C. elegans. The transcriptional and genetic data in this study demonstrate the functional diversity that can 49 develop within antiviral transcriptional responses in natural host populations. 50 Page 3 of 28 Background 51 The continuous battle between host and virus drives host genetic variation to arise in antiviral mechanisms such 52 as transcriptional responses. Regulatory genetic variation affects the viral susceptibility after infection, making 53 some individuals within the population more resistant than others [1-4]. Yet, the universality and mode-of-action 54 of genetic diversity in shaping antiviral transcriptional responses within natural populations remains largely 55 unknown. 56 Caenorhabditis elegans and its natural pathogen Orsay virus (OrV) are used as a powerful genetic 57 model system to study host-virus interactions [5]. OrV is a positive-sense single-stranded RNA virus infecting C. 58 elegans intestinal cells where it causes local disruptions of the cellular structures [5, 6]. Two major groups of 59 antiviral genes respond to viral infection in C. elegans: genes related to the RNA interference (RNAi) pathway 60 [5, 7-12] and genes related to the Intracellular Pathogen Response (IPR) [13-16]. The RNAi pathway activity is 61 controlled by the gene sta-1 which in turn is activated by the viral sensor sid-3 that is hypothesized to directly 62 interact with the Orsay virus [7]. Subsequently, the antiviral RNAi components dcr-1, drh-1, and rde-1 degrade 63 the viral RNA [9], but the RNAi genes themselves remain equally expressed during infection [9, 16]. The IPR 64 counteracts infection by intracellular pathogens (including OrV) and increases the ability to handle proteotoxic 65 stress [13-15]. The gene pals-22 co-operates together with pals-25 to control the IPR pathway by functioning as 66 a molecular switch between growth and antiviral defence. Pals-22 promotes development and lifespan, whereas 67 pals-25 stimulates pathogen resistance. Together pals-22 and pals-25 regulate a set of 80 genes that are 68 upregulated upon intracellular infection including 25 genes in the pals-family and several members of the 69 ubiquitination response [14, 15].. Both pals-22 and pals-25 do not change gene expression following OrV 70 infection. In total, the pals-gene family contains 39 members mostly found in five genetic clusters on 71 chromosome I, III, and V.. Recently, a third antiviral defence was identified which degrades the viral genome 72 after uridylation by the gene cde-1 [17]. Together, these antiviral pathways are key in controlling OrV infection 73 in C. elegans. 74The transcriptional responses following infection have so far been studied in the C. elegans laboratory 75 strain N2, in RNAi deficient mutants in the N2 background such as rde-1 and dcr-1 and in the RNAi-deficient 76 wild isolate JU1580 [7, 9, 10, 13, 14, 16]. These studies indica...

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“…Genes upregulated in JU2519 at 12 and 24 hr also showed a significant intersection with genes upregulated upon infection of nematodes with the microsporidia Nematocida parisii or the Orsay virus (Data S3; see genes GSEA tabs]). This overlap contained members of the pals gene family, previously shown to be a hallmark of microsporidia and viral infections [21,22,26,27]. Taken together, these results suggest that the transcriptional response to M. humicola shows some limited shared aspects with the response to infection by other pathogens.…”

Section: Resultsmentioning

confidence: 54%

Natural Infection of C. elegans by an Oomycete Reveals a New Pathogen-Specific Immune Response

et al. 2018

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In its natural habitat, the nematode Caenorhabditis elegans encounters a plethora of other organisms, including many that are pathogenic [1, 2]. The study of interactions between C. elegans and various pathogens has contributed to characterizing key mechanisms of innate immunity [2-4]. However, how C. elegans recognizes different pathogens to mount pathogen-specific immune responses remains still largely unknown [3, 5-8]. Expanding the range of known C. elegans-infecting pathogens and characterizing novel pathogen-specific immune responses are key steps toward answering this question. We report here that the oomycete Myzocytiopsis humicola is a natural pathogen of C. elegans, and we describe its infection strategy. We identify a new host immune response to pathogen exposure that involves induction of members of a previously uncharacterized gene family encoding chitinase-like (CHIL) proteins. We demonstrate that this response is highly specific against M. humicola and antagonizes the infection. We propose that CHIL proteins may diminish the ability of the oomycete to infect by hindering pathogen attachment to the host cuticle. This work expands our knowledge of natural eukaryotic pathogens of C. elegans and introduces a new pathosystem to address how animal hosts recognize and respond to oomycete infections.

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An Intracellular Pathogen Response Pathway Promotes Proteostasis in C. elegans

Cited by 97 publications

References 27 publications

A Model for Evolutionary Ecology of Disease: The Case for Caenorhabditis Nematodes and Their Natural Parasites

A Model for Evolutionary Ecology of Disease: The Case for Caenorhabditis Nematodes and Their Natural Parasites

Balancing selection of the Intracellular Pathogen Response in natural Caenorhabditis elegans populations

Natural Infection of C. elegans by an Oomycete Reveals a New Pathogen-Specific Immune Response

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