Βeta 2-glycoprotein I protects mice against gram-negative septicaemia in a sexually dimorphic manner

Abstract The immune responses of males and females to bacterial infections display differences. The mechanisms that underlie this sexual dimorphism are multifactorial. Lipopolysaccharide (LPS) contributes to the pathogenesis of endotoxaemia. We have previously demonstrated that the plasma protein be...

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Autores principales:	Fatima El-Assaad, Miao Qi, Alice Kizny Gordon, Jian Qi, Shangwen Dong, Freda Passam, James Crofton Weaver, Bill Giannakopoulos, Steven Anthony Krilis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/231b190675f34a56a24c456b8f06d775
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spelling	oai:doaj.org-article:231b190675f34a56a24c456b8f06d7752021-12-02T15:05:51ZΒeta 2-glycoprotein I protects mice against gram-negative septicaemia in a sexually dimorphic manner10.1038/s41598-017-07945-82045-2322https://doaj.org/article/231b190675f34a56a24c456b8f06d7752017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07945-8https://doaj.org/toc/2045-2322Abstract The immune responses of males and females to bacterial infections display differences. The mechanisms that underlie this sexual dimorphism are multifactorial. Lipopolysaccharide (LPS) contributes to the pathogenesis of endotoxaemia. We have previously demonstrated that the plasma protein beta-2 glycoprotein-1 (β2GPI) reduces LPS-induced inflammation in male mice. In the present study using a more robust infection model of septicaemia the role of β2GPI is examined in both male and female wild type (WT) and β2GPI deficient (β2GPI−/−) mice challenged with Escherichia coli (E. coli) intravenously. β2GPI deficiency led to an increase of E. coli colony forming units (CFU) in the circulation of both male and female mice. In male β2GPI−/− mice this was associated with a worse clinical severity score. This difference was not observed between female β2GPI−/− and female WT mice. Male WT mice had decreased levels of total and increased levels of free thiol β2GPI following administration of LPS or E. coli. This pattern of sexual dimorphic response was also observed in our cohort of humans with sepsis. These findings support a role for β2GPI in modulating the sex-specific susceptibility to gram-negative septicaemia.Fatima El-AssaadMiao QiAlice Kizny GordonJian QiShangwen DongFreda PassamJames Crofton WeaverBill GiannakopoulosSteven Anthony KrilisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fatima El-Assaad Miao Qi Alice Kizny Gordon Jian Qi Shangwen Dong Freda Passam James Crofton Weaver Bill Giannakopoulos Steven Anthony Krilis Βeta 2-glycoprotein I protects mice against gram-negative septicaemia in a sexually dimorphic manner
description	Abstract The immune responses of males and females to bacterial infections display differences. The mechanisms that underlie this sexual dimorphism are multifactorial. Lipopolysaccharide (LPS) contributes to the pathogenesis of endotoxaemia. We have previously demonstrated that the plasma protein beta-2 glycoprotein-1 (β2GPI) reduces LPS-induced inflammation in male mice. In the present study using a more robust infection model of septicaemia the role of β2GPI is examined in both male and female wild type (WT) and β2GPI deficient (β2GPI−/−) mice challenged with Escherichia coli (E. coli) intravenously. β2GPI deficiency led to an increase of E. coli colony forming units (CFU) in the circulation of both male and female mice. In male β2GPI−/− mice this was associated with a worse clinical severity score. This difference was not observed between female β2GPI−/− and female WT mice. Male WT mice had decreased levels of total and increased levels of free thiol β2GPI following administration of LPS or E. coli. This pattern of sexual dimorphic response was also observed in our cohort of humans with sepsis. These findings support a role for β2GPI in modulating the sex-specific susceptibility to gram-negative septicaemia.
format	article
author	Fatima El-Assaad Miao Qi Alice Kizny Gordon Jian Qi Shangwen Dong Freda Passam James Crofton Weaver Bill Giannakopoulos Steven Anthony Krilis
author_facet	Fatima El-Assaad Miao Qi Alice Kizny Gordon Jian Qi Shangwen Dong Freda Passam James Crofton Weaver Bill Giannakopoulos Steven Anthony Krilis
author_sort	Fatima El-Assaad
title	Βeta 2-glycoprotein I protects mice against gram-negative septicaemia in a sexually dimorphic manner
title_short	Βeta 2-glycoprotein I protects mice against gram-negative septicaemia in a sexually dimorphic manner
title_full	Βeta 2-glycoprotein I protects mice against gram-negative septicaemia in a sexually dimorphic manner
title_fullStr	Βeta 2-glycoprotein I protects mice against gram-negative septicaemia in a sexually dimorphic manner
title_full_unstemmed	Βeta 2-glycoprotein I protects mice against gram-negative septicaemia in a sexually dimorphic manner
title_sort	βeta 2-glycoprotein i protects mice against gram-negative septicaemia in a sexually dimorphic manner
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/231b190675f34a56a24c456b8f06d775
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Βeta 2-glycoprotein I protects mice against gram-negative septicaemia in a sexually dimorphic manner

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