Role of human alveolar macrophages in SARS-CoV-2 infection (B06)

• Subject Area: Pneumology, Thoracic Surgery
• Term: from 2014 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 114933180

SARS-CoV-2 utilizes ACE2 as essential cellular entry receptor. Studies have suggested abundant ACE2 expression in the human lung, inferring strong permissiveness to SARS-CoV-2 infection with resultant lung injury. Against this expectation, we provide evidence that ACE2 expression must be considered scarce, thereby limiting SARS-CoV-2 propagation in human alveoli. Instead, spectral imaging of ex vivo infected human lungs and COVID-19 autopsy samples depicted that alveolar macrophages were frequently positive for SARS-CoV-2, indicating viral endocytosis. First data on single-cell sequencing of SARS-CoV-2 infected human lung tissue confirms the predominant viral intake into myeloid cells. We therefore hypothesize that direct damage of alveolar epithelial cells by SARS-CoV-2 infection is less likely rather than a strong intake of virions into myeloid cells leading to a strong inflammatory activation, which might foster severe courses of COVID-19.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 84: Innate Immunity of the Lung: Mechanisms of Pathogen Attack and Host Defence in Pneumonia
• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Project Heads: Professorin Dr. Haike Antelmann, until 6/2022; Professor Dr. Stefan Hippenstiel; Professor Dr. Andreas Hocke