Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Sex-related differences in gene expression following Coxiella burnetii infection: potential role of circadian rhythm

ABSTRACT: Q fever, a zoonosis due to Coxiella burnetii infection, exhibits sexual dimorphism; men are affected more frequently and severely than women for a given exposure. Here we explore whether the severity of C. burnetii infection in mice is related to differences in male and female gene expression profiles. Mice were infected with C. burnetii for 24 hours, and gene expression was measured in liver cells using microarrays. Multiclass analysis identified 2,777 probes for which expression was specifically modulated by C. burnetti infection. Only 14% of the modulated genes were sex-independent, and the remaining 86% were differentially expressed in males and females. Castration of males and females showed that sex hormones were responsible for more than 60% of the observed gene modulation, and this reduction was most pronounced in males. Using functional annotation of modulated genes, we identified four clusters enriched in males that were related to cell-cell adhesion, signal transduction, defensins and cytokine/Jak-Stat pathways. Up-regulation of the IL-10 and Stat-3 genes may account for the high susceptibility of men with Q fever to C. burnetii infection and autoantibody production. Two clusters were identified in females, including the circadian rhythm pathway, which consists of positive (Clock, Arntl) and negative (Per) limbs of a feedback loop. We found that Clock and Arntl were down-modulated whereas Per was up-regulated; these changes may be associated with efficient bacterial elimination in females but not in males, in which an exacerbated host response would be prominent. This large-scale study revealed for the first time that circadian rhythm plays a major role in the anti-infectious response of mice, and it provides a new basis for elucidating the role of sexual dimorphism in human infections. Liver transcriptome was analyzed using whole genome microarray. Forty mice were divided into 8 groups of five mice upon three binary factors: sex, infection and castration. Four Samples were excluded from final analysis (see Data Processing for additional details).

ORGANISM(S): Mus musculus

SUBMITTER: Didier Raoult

PROVIDER: E-GEOD-21065 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Sex-related differences in gene expression following Coxiella burnetii infection in mice: potential role of circadian rhythm.

Textoris Julien J Ban Leang Heng LH Capo Christian C Raoult Didier D Leone Marc M Mege Jean-Louis JL

PloS one 20100813 8

<h4>Background</h4>Q fever, a zoonosis due to Coxiella burnetii infection, exhibits sexual dimorphism; men are affected more frequently and severely than women for a given exposure. Here we explore whether the severity of C. burnetii infection in mice is related to differences in male and female gene expression profiles.<h4>Methodology/principal findings</h4>Mice were infected with C. burnetii for 24 hours, and gene expression was measured in liver cells using microarrays. Multiclass analysis id ...[more]

PMID: 20730052

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Project description:Despite sharing much of their genomes, males and females are often highly dimorphic, reflecting at least in part the resolution of sexual conflict in response to sexually antagonistic selection. Sexual dimorphism arises owing to sex differences in gene expression, and steroid hormones are often invoked as a proximate cause of sexual dimorphism. Experimental elevation of androgens can lead to masculinization of behavior, physiology, and gene expression, but knowledge of the role of hormones remains incomplete, including how the sexes differ in their gene expression in response to exposure to hormones. We addressed these questions in a bird species with a long history of behavioral endocrinological and ecological study, the dark-eyed junco (Junco hyemalis), using a species-specific microarray. Focusing on two brain regions involved in sexually dimorphic behavior and regulation of hormone secretion, we identified 1,639 genes that differed in expression by sex in the ventromedial telencephalon and 768 in hypothalamus. In response to experimentally elevated testosterone, females exhibited a more “male-like” expression pattern than control females; unexpectedly, male expression patterns became more “female-like” rather than hyper-masculinized when compared to control males. This sex difference in pattern arose both because testosterone altered regulation of different genes in each sex and because testosterone altered regulation of the same genes differentially, i.e., up in one sex, down in the other. Hormonally regulated gene expression is a key genetic and physiological mechanism underlying sexual dimorphism, and further study should help to explain how it relates to the resolution of sexual conflict. Hypothalamus: 24 samples were analyzed, all were biological (not technical) replicates. 6 from males treated with testosterone [MT], 6 from control males [MC], 6 from females treated with testosterone [FT], and 6 from control females [FC]. All hybridizations were paired, and all treatment groups were compared, but no sample was analyzed more than once. Ventromedial telencephalon: 24 samples were analyzed, all were biological (not technical) replicates. 6 from males treated with testosterone [MT], 6 from control males [MC], 6 from females treated with testosterone [FT], and 6 from control females [FC]. All hybridizations were paired, and all treatment groups were compared, but no sample was analyzed more than once.

Dataset Information

Sex-related differences in gene expression following Coxiella burnetii infection: potential role of circadian rhythm

Publications

Sex-related differences in gene expression following Coxiella burnetii infection in mice: potential role of circadian rhythm.

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