DAF-16-Dependent Suppression of Immunity During Reproduction in <i>Caenorhabditis elegans</i>

Miyata, Sachiko; Begun, Jakob; Troemel, Emily R.; Ausubel, Frederick M.

doi:10.1534/genetics.107.083923

Cited by 95 publications

(129 citation statements)

References 81 publications

(114 reference statements)

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“…However, the mechanisms through which this protection was conferred differed between the two bacteria. For BM, enhanced resistance was linked to decreased reproduction, similar to the case of numerous mutants with compromised fecundity (31). For PM, enhanced resistance was independent of reproduction; instead, it was found to be associated with pmk-1-dependent immune gene expression and was abolished by pmk-1 disruption.…”

Section: Discussionmentioning

confidence: 74%

Association with Soil Bacteria Enhances p38-Dependent Infection Resistance in Caenorhabditis elegans

et al. 2013

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The importance of our inner microbial communities for proper immune responses against invading pathogens is now well accepted, but the mechanisms underlying this protection are largely unknown. In this study, we used Caenorhabditis elegans to investigate such mechanisms. Since very little is known about the microbes interacting with C. elegans in its natural environment, we began by taking the first steps to characterize the C. elegans microbiota. We established a natural-like environment in which initially germfree, wild-type larvae were grown on enriched soil. Bacterial members of the adult C. elegans microbiota were isolated by culture and identified using 16S rRNA gene sequencing. Using pure cultures of bacterial isolates as food, we identified two, Bacillus megaterium and Pseudomonas mendocina, that enhanced resistance to a subsequent infection with the Gram-negative pathogen Pseudomonas aeruginosa. Whereas protection by B. megaterium was linked to impaired egg laying, corresponding to a known trade-off between fecundity and resistance, the mechanism underlying protection conferred by P. mendocina depended on weak induction of immune genes regulated by the p38 MAPK pathway. Disruption of the p38 ortholog, pmk-1, abolished protection. P. mendocina enhanced resistance to P. aeruginosa but not to the Gram-positive pathogen Enterococcus faecalis. Furthermore, protection from P. aeruginosa was similarly induced by a P. aeruginosa gacA mutant with attenuated virulence but not by a different C. elegans-associated Pseudomonas sp. isolate. Our results support a pivotal role for the conserved p38 pathway in microbiota-initiated immune protection and suggest that similarity between microbiota members and pathogens may play a role in such protection.

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Section: Discussionmentioning

confidence: 74%

Association with Soil Bacteria Enhances p38-Dependent Infection Resistance in Caenorhabditis elegans

et al. 2013

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“…In brief, the rationale for using the glp-4; sek-1 mutant nematodes instead of wild-type animals is that wild-type C. elegans produces many offspring which confounds killing assays, both because it is difficult to determine progeny from adults and because larvae often hatch inside the nematode, leading to death of the worm by a mechanism not directly related to pathogen exposure (so-called matricidal killing). C. elegans glp-4 mutant animals are unable to produce gonads or progeny at 25°C and thus are suited for these studies; however, sterile animals are long-lived compared to wild-type animals (39). C. elegans SEK-1 encodes a conserved mitogen-activated protein (MAP) kinase kinase involved in the innate immune response, and sek-1 animals are relatively immunocompromised (28).…”

Section: Methodsmentioning

confidence: 99%

Candida albicans Hyphal Formation and Virulence Assessed Using a Caenorhabditis elegans Infection Model

et al. 2009

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Candida albicans colonizes the human gastrointestinal tract and can cause life-threatening systemic infection in susceptible hosts. We study here C. albicans virulence determinants using the nematode Caenorhabditis elegans in a pathogenesis system that models candidiasis. The yeast form of C. albicans is ingested into the C. elegans digestive tract. In liquid media, the yeast cells then undergo morphological change to form hyphae, which results in aggressive tissue destruction and death of the nematode. Several lines of evidence demonstrate that hyphal formation is critical for C. albicans pathogenesis in C. elegans. First, two yeast species unable to form hyphae (Debaryomyces hansenii and Candida lusitaniae) were less virulent than C. albicans in the C. elegans assay. Second, three C. albicans mutant strains compromised in their ability to form hyphae (efg1⌬/efg1⌬, flo8⌬/flo8⌬, and cph1⌬/cph1⌬ efg1⌬/efg1⌬) were dramatically attenuated for virulence. Third, the conditional tet-NRG1 strain, which enables the external manipulation of morphogenesis in vivo, was more virulent toward C. elegans when the assay was conducted under conditions that permit hyphal growth. Finally, we demonstrate the utility of the C. elegans assay in a screen for C. albicans virulence determinants, which identified several genes important for both hyphal formation in vivo and the killing of C. elegans, including the recently described CAS5 and ADA2 genes. These studies in a C. elegans-C. albicans infection model provide insights into the virulence mechanisms of an important human pathogen.Candida albicans is the most common human fungal pathogen; however, our knowledge of its virulence mechanisms is incomplete, and our best antifungal agents are often ineffective in treating severe candidiasis (3). Infections with Candida species account for 70 to 90% of all invasive mycoses (32) and can be associated with devastating consequences, particularly in intensive care units where mortality rates reach 40% (24, 34). The drug resistance of pathogenic fungi exacerbates this problem and often limits therapeutic options (35). The identification of virulence pathways that can be targeted with novel antifungal therapies is urgently needed (31,38,46).One approach to understand the genetic mechanisms of virulence is to use invertebrates, such as the nematode Caenorhabditis elegans, as model hosts (43). Studies of C. elegans infection with Pseudomonas aeruginosa and Cryptococcus neoformans, for example, have led to the identification of evolutionarily conserved mechanisms of host immunity and microbial virulence (1, 21, 50). However, efforts to design an accurate nonmammalian model of C. albicans pathogenesis have been stymied, in part because it has been difficult to capture the role of Candida dimorphism in these systems.Morphogenesis in C. albicans is intricately related to pathogenesis and thus has been intensively studied. C. albicans hyphae are important for tissue destruction and host invasion (3). As such, C. albicans mutants and non-albicans Cand...

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“…For example, most of the worms expressing fshr-1(ϩ) in neurons produce virtually no embryos when they are fed PA14; in contrast, control worms and worms expressing fshr-1(ϩ) under the control of the fshr-1 or ges-1 promoters produce large quantities of embryos. Sterility has been shown to cause significant pathogen resistance in C. elegans (22), so it is possible that the apparent sterility caused by neuronally expressed fshr-1(ϩ) may lead to the partial suppression of fshr-1(ok778) pathogen sensitivity, rather than a more specific role for neuronal FSHR-1 in pathogen defense. Regardless of whether FSHR-1 can function in the neurons, the strong suppression of the Fold change in basal expression was calculated as the ratio of wild-type expression to mutant expression in worms fed OP50.…”

Section: Fshr-1 Regulates a Set Of Pa14-response Genesmentioning

confidence: 99%

The G protein-coupled receptor FSHR-1 is required for the Caenorhabditis elegans innate immune response

Powell

Kim

Ausubel

2009

Proc. Natl. Acad. Sci. U.S.A.

116

138

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Innate immunity is an ancient defense system used by both vertebrates and invertebrates. Previously characterized innate immune responses in plants and animals are triggered by detection of pathogens using specific receptors, which typically use a leucine-rich repeat (LRR) domain to bind molecular patterns associated with infection. The nematode Caenorhabditis elegans uses defense pathways conserved with vertebrates; however, the mechanism by which C. elegans detects pathogens is unknown. We screened all LRR-containing transmembrane receptors in C. elegans and identified the G proteincoupled receptor FSHR-1 as an important component of the C. elegans immune response to Gram-negative and Gram-positive bacterial pathogens. FSHR-1 acts in the C. elegans intestine, the primary site of exposure to ingested pathogens. FSHR-1 signals in parallel to the known p38 MAPK pathway but converges to regulate the transcriptional induction of an overlapping but nonidentical set of antimicrobial effectors. FSHR-1 may act generally to boost the nematode immune response, or it may function as a pathogen receptor.host-pathogen interactions ͉ leucine-rich repeat

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DAF-16-Dependent Suppression of Immunity During Reproduction in Caenorhabditis elegans

Cited by 95 publications

References 81 publications

Association with Soil Bacteria Enhances p38-Dependent Infection Resistance in Caenorhabditis elegans

Association with Soil Bacteria Enhances p38-Dependent Infection Resistance in Caenorhabditis elegans

Candida albicans Hyphal Formation and Virulence Assessed Using a Caenorhabditis elegans Infection Model

The G protein-coupled receptor FSHR-1 is required for the Caenorhabditis elegans innate immune response

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