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Deficiency of Tlr7 and Irf7 increases the severity of COVID-19 through the reduced interferon production [scRNA-seq]

GSE274686 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/08/20 Platform GPL30172
Summary
Toll-like receptor 7 (Tlr7) deficiency-accelerated severe COVID-19 is associated with reduced production of interferons (IFNs). However, the underlying mechanisms remain elusive. Here, we demonstrate that the deficiency of Tlr7 and Irf7 globally and/or in immune cells in mice increases the severity of COVID-19 via impaired IFN activation in both immune and/or non-immune cells, leading to increased lung viral loads. These effects are associated with reduced IFN alpha and gamma production. The deficiency of Tlr7 in the infected mice tends to cause the reduced production and nuclear translocation of Interferon regulatory factor 7 (IRF7), indicative of reduced IRF7 activation. Despite higher amounts of lung viral antigen, Tlr7 or Irf7 deficiency resulted in substantially reduced production of antibodies against SARS-CoV-2, thereby delaying the viral clearance. These results highlight the importance of the activation of TLR7 and IRF7, leading to IFN production on the development of innate and adaptive immunity against COVID-19.
Published in
Deficiency of Tlr7 and Irf7 in mice increases the severity of COVID-19 through the reduced interferon production
Wang C, Khatun MS, Ellsworth CR et al. · Communications biology 2024 · PMID 39289468 · doi:10.1038/s42003-024-06872-5
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Also filed as BioProject PRJNA1147662 and SRA study SRP526060. Searching any of these in the dataset finder brings you back here.

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