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

<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 an...

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Autores principales:	Julien Textoris, Leang Heng Ban, Christian Capo, Didier Raoult, Marc Leone, Jean-Louis Mege
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d00c77f899264305b6f9c86fc2574421
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spelling	oai:doaj.org-article:d00c77f899264305b6f9c86fc25744212021-11-18T06:36:06ZSex-related differences in gene expression following Coxiella burnetii infection in mice: potential role of circadian rhythm.1932-620310.1371/journal.pone.0012190https://doaj.org/article/d00c77f899264305b6f9c86fc25744212010-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20730052/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<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 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.<h4>Conclusion</h4>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.Julien TextorisLeang Heng BanChristian CapoDidier RaoultMarc LeoneJean-Louis MegePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 8, p e12190 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julien Textoris Leang Heng Ban Christian Capo Didier Raoult Marc Leone Jean-Louis Mege Sex-related differences in gene expression following Coxiella burnetii infection in mice: potential role of circadian rhythm.
description	<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 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.<h4>Conclusion</h4>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.
format	article
author	Julien Textoris Leang Heng Ban Christian Capo Didier Raoult Marc Leone Jean-Louis Mege
author_facet	Julien Textoris Leang Heng Ban Christian Capo Didier Raoult Marc Leone Jean-Louis Mege
author_sort	Julien Textoris
title	Sex-related differences in gene expression following Coxiella burnetii infection in mice: potential role of circadian rhythm.
title_short	Sex-related differences in gene expression following Coxiella burnetii infection in mice: potential role of circadian rhythm.
title_full	Sex-related differences in gene expression following Coxiella burnetii infection in mice: potential role of circadian rhythm.
title_fullStr	Sex-related differences in gene expression following Coxiella burnetii infection in mice: potential role of circadian rhythm.
title_full_unstemmed	Sex-related differences in gene expression following Coxiella burnetii infection in mice: potential role of circadian rhythm.
title_sort	sex-related differences in gene expression following coxiella burnetii infection in mice: potential role of circadian rhythm.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/d00c77f899264305b6f9c86fc2574421
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Sex-related differences in gene expression following Coxiella burnetii infection in mice: potential role of circadian rhythm.

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