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- W3215903599 abstract "Apart from clinical data, mouse models for SARS have helped advance our knowledge in fighting against COVID-19. We emphasised on a physiological model of infection and host-compatibility and used the murine coronavirus mCoV-A59, which belongs to the same subgroup as SARS-CoV-2. Thus, we could mimic asymptomatic infections with an immune response that results in major virus clearance at day 10 post infection. Using histology, multi-colour flow cytometry and RNAseq of mCoV infected lungs, we were able to detect an intriguing temporal interplay of innate and adaptive immunity in virus resolution. Virus clearance was already evident after 4 days and RNAseq revealed the unexpectedly crucial role of innate immune cell regulation, being strongest regulated cellular pathway. Moreover, interferon type I signalling was also remarkably upregulated during this early phase; a hallmark of SARS-CoV infections and mainly produced by innate immune cells. Lung cell apoptosis was highest at day 10, at which we could also observe a distinct increase in cytotoxic CD8 T cells. This indicates that successful, rapid SARS-CoV clearance depends mainly on innate immunity rather than on adaptive responses, while at a later phase recruited CD8 T cells contribute to lung tissue damage. This early innate immune response might explain the observed decline of SARS-CoV-2 antibodies in asymptomatic or mild infections. Thus, we highlight the importance to strengthen the innate immune system at the beginning of a SARS-CoV infection with the requirement to dampen CD8 T cell function. Lastly, our model allows screening of compounds modulating the innate and adaptive immunity during disease." @default.
- W3215903599 created "2021-12-06" @default.
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- W3215903599 date "2021-09-05" @default.
- W3215903599 modified "2023-09-27" @default.
- W3215903599 title "Immunological and transcriptional characterisation of SARS-CoV infected mouse lungs" @default.
- W3215903599 doi "https://doi.org/10.1183/13993003.congress-2021.pa3618" @default.
- W3215903599 hasPublicationYear "2021" @default.
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