RT Journal Article
SR Electronic
T1 Immunological and transcriptional characterisation of SARS-CoV infected mouse lungs
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA3618
DO 10.1183/13993003.congress-2021.PA3618
VO 58
IS suppl 65
A1 Salzmann, Manuel
A1 Haider, Patrick
A1 Plasenzotti, Roberto
A1 Wojta, Johann
A1 Hohensinner, Philipp
YR 2021
UL http://erj.ersjournals.com/content/58/suppl_65/PA3618.abstract
AB 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.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA3618.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).