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| Item Type: | Article |
|---|---|
| Title: | Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19 |
| Creators: |
Nouailles, G.  ORCID: https://orcid.org/0000-0003-1973-3119, Wyler, E. ORCID: https://orcid.org/0000-0002-9884-1806, Pennitz, P. ORCID: https://orcid.org/0000-0002-8132-7237, Postmus, D. ORCID: https://orcid.org/0000-0002-9551-0411, Vladimirova, D., Kazmierski, J. ORCID: https://orcid.org/0000-0002-7962-2165, Pott, F. ORCID: https://orcid.org/0000-0003-3700-1691, Dietert, K. ORCID: https://orcid.org/0000-0002-5667-6750, Muelleder, M., Farztdinov, V., Obermayer, B. ORCID: https://orcid.org/0000-0002-9116-630X, Wienhold, S.M. ORCID: https://orcid.org/0000-0001-5655-4350, Andreotti, S., Hoefler, T. ORCID: https://orcid.org/0000-0001-7486-5582, Sawitzki, B., Drosten, C. ORCID: https://orcid.org/0000-0001-7923-0519, Sander, L.E. ORCID: https://orcid.org/0000-0002-0476-9947, Suttorp, N., Ralser, M., Beule, D. ORCID: https://orcid.org/0000-0002-3284-0632, Gruber, A.D. ORCID: https://orcid.org/0000-0002-4502-0393, Goffinet, C. ORCID: https://orcid.org/0000-0002-3959-004X, Landthaler, M. ORCID: https://orcid.org/0000-0002-1075-8734, Trimpert, J. ORCID: https://orcid.org/0000-0003-1616-0810 and Witzenrath, M.
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| Abstract: | In COVID-19, immune responses are key in determining disease severity. However, cellular mechanisms at the onset of inflammatory lung injury in SARS-CoV-2 infection, particularly involving endothelial cells, remain ill-defined. Using Syrian hamsters as a model for moderate COVID-19, we conduct a detailed longitudinal analysis of systemic and pulmonary cellular responses, and corroborate it with datasets from COVID-19 patients. Monocyte-derived macrophages in lungs exert the earliest and strongest transcriptional response to infection, including induction of pro-inflammatory genes, while epithelial cells show weak alterations. Without evidence for productive infection, endothelial cells react, depending on cell subtypes, by strong and early expression of anti-viral, pro-inflammatory, and T cell recruiting genes. Recruitment of cytotoxic T cells as well as emergence of IgM antibodies precede viral clearance at day 5 post infection. Investigating SARS-CoV-2 infected Syrian hamsters thus identifies cell type-specific effector functions, providing detailed insights into pathomechanisms of COVID-19 and informing therapeutic strategies. |
| Keywords: | Alveolar Epithelial Cells, Animal Disease Models, COVID-19, Cytokines, Cytotoxic T-Lymphocytes, Endothelial Cells, Immunoglobulin M, Inflammation, Lung, Macrophages, Monocytes, SARS-CoV-2, Signal Transduction, Toll-Like Receptors, Animals, Cricetinae, Mesocricetus |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 12 |
| Number: | 1 |
| Page Range: | 4869 |
| Date: | 11 August 2021 |
| Official Publication: | https://doi.org/10.1038/s41467-021-25030-7 |
| PubMed: | View item in PubMed |
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