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Deficiency of Tlr7 and Irf7 increases the severity of COVID-19 through the reduced interferon production

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE274586 | GEO | 2024/09/05

REPOSITORIES: GEO

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

Project description: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.

2024-08-20 | GSE274686 | GEO

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