作者
Geraldine Nouailles,Emanuel Wyler,Peter Pennitz,Dylan Postmus,Daria Vladimirova,Julia Kazmierski,Fabian Pott,Kristina Dietert,Michael Mülleder,Vadim Farztdinov,Benedikt Obermayer,Sandra-Maria Wienhold,Sandro Andreotti,Thomas Hoefler,Birgit Sawitzki,Christian Drosten,Leif Erik Sander,Norbert Suttorp,Markus Ralser,Dieter Beule,Achim D. Gruber,Christine Goffinet,Markus Landthaler,Jakob Trimpert,Martin Witzenrath
摘要
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.