Artikel ; Online: Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19.
2021 Band 12, Seite(n) 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. |
|---|---|
| Mesh-Begriff(e) | 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 |
| Chemische Substanzen | Interferon Type I ; RNA, Viral ; Receptors, Pattern Recognition ; TLR7 protein, human ; Toll-Like Receptor 7 |
| Sprache | Englisch |
| Erscheinungsdatum | 2021-11-11 |
| Erscheinungsland | Switzerland |
| Dokumenttyp | Journal Article |
| ZDB-ID | 2606827-8 |
| ISSN | 1664-3224 ; 1664-3224 |
| ISSN (online) | 1664-3224 |
| ISSN | 1664-3224 |
| DOI | 10.3389/fimmu.2021.756262 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
Zusatzmaterialien
Kategorien
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.