Sex-Dependent Resistance to the Pathogenic Fungus <i>Cryptococcus neoformans</i>

Berg, Maaike C. W. van den; Woerlee, Jessica Z.; Ma, Hansong; May, Robin C.

doi:10.1534/genetics.106.056093

Cited by 38 publications

(24 citation statements)

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“…We and others have previously demonstrated that different Caenorhabditis species exhibit significantly different lifespans [21], [22]. Since different laboratory isolates can exhibit variation in lifespan [23], we conducted parallel longevity assays on our isolates of C. elegans N2, C. briggsae AF16, C. remanei EM464 and C. brenneri CB5161.…”

Section: Resultsmentioning

confidence: 99%

“…We note that the presence of both males and females within the gonochoristic population could mean that enhanced daf-16 expression may be restricted to one or other gender, but given that both male and female animals in the gonochoristic species are longer lived than either gender of C. elegans or C. briggsae [21], we regard it as more likely that daf-16 is highly expressed in both genders of the gonochoristic species.…”

Section: Resultsmentioning

confidence: 99%

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Phenotypic Covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

2010

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BackgroundAgeing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulin–like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species.Methodology/Principal FindingsWe show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis.ConclusionsThe gonochoristic species display a significantly longer lifespan (p<0.0001) and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Phenotypic Covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

2010

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“…In support of this hypothesis, there is growing evidence in favour of sex-dependent activity of this pathway. In C. elegans, males are both the longer-lived (50,51) and more-pathogen-resistant (91) sex. Importantly, however, both effects are completely lost in daf-16 knockout males, (50,91) suggesting that the enhanced lifespan of male C. elegans may result from constitutive activation of DAF-16.…”

Section: Stress Responses and Longevitymentioning

confidence: 99%

Gender, immunity and the regulation of longevity

May

2007

BioEssays

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For humans and many other animals, gender is a fact of life. Most individuals are born either male or female and their sex will have an enormous influence on their behaviour, physiology and life history. In this review, I consider the effect gender has on lifespan. In particular, I discuss the role played by behaviour, immunity and oxidative damage in determining sex-dependent differences in longevity. I consider existing explanations for the effect of gender on lifespan and how these explanations fit together. Finally, I expand on the recent suggestion of a key role for the insulin/IGF-1 signalling pathway in regulating sex-dependent differences in lifespan and I highlight a number of areas for future investigation.

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“…This resistance can be induced in hermaphrodites by inappropriate activation of the male sex determination pathway. These differences are molecularly determined and may not result from behavioral changes or reproductive differences (33).…”

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confidence: 99%

The DM Domain Transcription Factor MAB-3 Regulates Male Hypersensitivity to Oxidative Stress in Caenorhabditis elegans

Inoue

Nishida

2010

Molecular and Cellular Biology

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Sex differences occur in most species and involve a variety of biological characteristics. The nematodeCaenorhabditis elegans consists of two sexes, self-fertile hermaphrodites (XX) and males (XO). Males differ from hermaphrodites in morphology, behavior, and life span. Here, we find that male C. elegans worms are much more sensitive than hermaphrodites to oxidative stress and show that the DM domain transcription factor MAB-3 plays a pivotal role in determining this male hypersensitivity. The hypersensitivity to oxidative stress does not depend on the dosage of X chromosomes but is determined by the somatic sex determination pathway. Our analyses show that the male hypersensitivity is controlled by MAB-3, one of the downstream effectors of the master terminal switch TRA-1 in the sex determination pathway. Moreover, we find that MAB-3 suppresses expression of several transcriptional target genes of the ELT-2 GATA factor, which is a global regulator of transcription in the C. elegans intestine, and show that RNA interference (RNAi) against elt-2 increases sensitivity to oxidative stress. These results strongly suggest that the DM domain protein MAB-3 regulates oxidative stress sensitivity by repressing transcription of ELT-2 target genes in the intestine.Sex differences occur in most species and not only create male or female gametes but also affect a variety of somatic traits, including morphology, behavior, and life history. In addition, there are often differences between the sexes in terms of disease susceptibility (23), many of which cannot be explained in terms of behavioral or anatomical differences. Most of these sexual dimorphisms are thought to be controlled by differences in gene regulation in each sex.The nematode Caenorhabditis elegans is widely used as an experimental multicellular organism. C. elegans occurs as a population comprising self-fertilizing hermaphrodites that are diploid for the X chromosome and a low percentage of males that possess a single X chromosome. Males are produced either as a result of nondisjunction of the X chromosomes during gametogenesis in the hermaphrodite or from a male-hermaphrodite mating. All somatic differences between the sexes result from the differential activity of a "global" sex determination regulatory pathway that is controlled by the number of X chromosomes. A series of inhibitory interactions in this signal transduction pathway ultimately sets the activity of the terminal transcription factor tra-1. The hermaphrodite fate is specified when TRA-1 is active, and the male fate is specified when TRA-1 is inactive. It has been suggested that TRA-1 regulates transcription of sex differentiation genes and determines somatic sexual fate cell autonomously (37).C. elegans males are morphologically distinct from hermaphrodites: the male body is thinner, and the tail is specialized to deliver sperm to the hermaphrodite during mating. There are also behavioral differences between the sexes. Males are more active and engage in mate searching and frequent "backing" behav...

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Sex-Dependent Resistance to the Pathogenic Fungus Cryptococcus neoformans

Cited by 38 publications

References 38 publications

Phenotypic Covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

Phenotypic Covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes

Gender, immunity and the regulation of longevity

The DM Domain Transcription Factor MAB-3 Regulates Male Hypersensitivity to Oxidative Stress in Caenorhabditis elegans

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