Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19

A male sex bias has emerged in the COVID-19 pandemic, fitting to the sex-biased pattern in other viral infections. Males are 2.84 times more often admitted to the ICU and mortality is 1.39 times higher as a result of COVID-19. Various factors play a role in this, and novel studies suggest that the g...

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Autores principales:	Anna E. Spiering, Teun J. de Vries
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	TLR7 interferon COVID-19 X chromosome inactivation escape gene-dose effect sex differences Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/affeedb047b149a7b87d0b479f0d5ae1
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spelling	oai:doaj.org-article:affeedb047b149a7b87d0b479f0d5ae12021-11-11T06:44:13ZWhy Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-191664-322410.3389/fimmu.2021.756262https://doaj.org/article/affeedb047b149a7b87d0b479f0d5ae12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.756262/fullhttps://doaj.org/toc/1664-3224A male sex bias has emerged in the COVID-19 pandemic, fitting to the sex-biased pattern in other viral infections. Males are 2.84 times more often admitted to the ICU and mortality is 1.39 times higher as a result of COVID-19. Various factors play a role in this, and novel studies suggest that the gene-dose of Toll-Like Receptor (TLR) 7 could contribute to the sex-skewed severity. TLR7 is one of the crucial pattern recognition receptors for SARS-CoV-2 ssRNA and the gene-dose effect is caused by X chromosome inactivation (XCI) escape. Female immune cells with TLR7 XCI escape have biallelic TLR7 expression and produce more type 1 interferon (IFN) upon TLR7 stimulation. In COVID-19, TLR7 in plasmacytoid dendritic cells is one of the pattern recognition receptors responsible for IFN production and a delayed IFN response has been associated with immunopathogenesis and mortality. Here, we provide a hypothesis that females may be protected to some extend against severe COVID-19, due to the biallelic TLR7 expression, allowing them to mount a stronger and more protective IFN response early after infection. Studies exploring COVID-19 treatment via the TLR7-mediated IFN pathway should consider this sex difference. Various factors such as age, sex hormones and escape modulation remain to be investigated concerning the TLR7 gene-dose effect.Anna E. SpieringAnna E. SpieringTeun J. de VriesTeun J. de VriesFrontiers Media S.A.articleTLR7interferonCOVID-19X chromosome inactivation escapegene-dose effectsex differencesImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	TLR7 interferon COVID-19 X chromosome inactivation escape gene-dose effect sex differences Immunologic diseases. Allergy RC581-607
spellingShingle	TLR7 interferon COVID-19 X chromosome inactivation escape gene-dose effect sex differences Immunologic diseases. Allergy RC581-607 Anna E. Spiering Anna E. Spiering Teun J. de Vries Teun J. de Vries Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19
description	A male sex bias has emerged in the COVID-19 pandemic, fitting to the sex-biased pattern in other viral infections. Males are 2.84 times more often admitted to the ICU and mortality is 1.39 times higher as a result of COVID-19. Various factors play a role in this, and novel studies suggest that the gene-dose of Toll-Like Receptor (TLR) 7 could contribute to the sex-skewed severity. TLR7 is one of the crucial pattern recognition receptors for SARS-CoV-2 ssRNA and the gene-dose effect is caused by X chromosome inactivation (XCI) escape. Female immune cells with TLR7 XCI escape have biallelic TLR7 expression and produce more type 1 interferon (IFN) upon TLR7 stimulation. In COVID-19, TLR7 in plasmacytoid dendritic cells is one of the pattern recognition receptors responsible for IFN production and a delayed IFN response has been associated with immunopathogenesis and mortality. Here, we provide a hypothesis that females may be protected to some extend against severe COVID-19, due to the biallelic TLR7 expression, allowing them to mount a stronger and more protective IFN response early after infection. Studies exploring COVID-19 treatment via the TLR7-mediated IFN pathway should consider this sex difference. Various factors such as age, sex hormones and escape modulation remain to be investigated concerning the TLR7 gene-dose effect.
format	article
author	Anna E. Spiering Anna E. Spiering Teun J. de Vries Teun J. de Vries
author_facet	Anna E. Spiering Anna E. Spiering Teun J. de Vries Teun J. de Vries
author_sort	Anna E. Spiering
title	Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19
title_short	Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19
title_full	Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19
title_fullStr	Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19
title_full_unstemmed	Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19
title_sort	why females do better: the x chromosomal tlr7 gene-dose effect in covid-19
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/affeedb047b149a7b87d0b479f0d5ae1
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Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19

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