Article ; Online: Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19.
2021 Volume 12, Page(s) 756262
Abstract: 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 ...
| Abstract | 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. |
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| MeSH term(s) | COVID-19/mortality ; COVID-19/pathology ; Chromosomes, Human, X/genetics ; Critical Care/statistics & numerical data ; Dendritic Cells/immunology ; Female ; Gene Dosage/genetics ; Humans ; Interferon Type I/biosynthesis ; Interferon Type I/immunology ; Male ; RNA, Viral/genetics ; Receptors, Pattern Recognition/genetics ; Receptors, Pattern Recognition/metabolism ; Risk Factors ; SARS-CoV-2/immunology ; Sex Factors ; Signal Transduction/immunology ; Toll-Like Receptor 7/genetics ; Toll-Like Receptor 7/metabolism ; X Chromosome Inactivation/genetics ; COVID-19 Drug Treatment |
| Chemical Substances | Interferon Type I ; RNA, Viral ; Receptors, Pattern Recognition ; TLR7 protein, human ; Toll-Like Receptor 7 |
| Language | English |
| Publishing date | 2021-11-11 |
| Publishing country | Switzerland |
| Document type | Journal Article |
| ZDB-ID | 2606827-8 |
| ISSN | 1664-3224 ; 1664-3224 |
| ISSN (online) | 1664-3224 |
| ISSN | 1664-3224 |
| DOI | 10.3389/fimmu.2021.756262 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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