SARS-CoV-2 Spike Protein Activates Human Lung Macrophages

Abstract: COVID-19 is a viral disease caused by SARS-CoV-2. This disease is characterized primarily,but not exclusively, by respiratory tract inflammation. SARS-CoV-2 infection relies on the binding ofspike protein to ACE2 on the host cells. The virus uses the protease TMPRSS2 as an entry activator.Human lung macrophages (HLMs) are the most abundant immune cells in the lung and fulfill avariety of specialized functions mediated by the production of cytokines and chemokines. The aim ofthis project was to investigate the effects of spike protein on HLM activation and the expression ofACE2 and TMPRSS2 in HLMs. Spike protein induced CXCL8, IL-6, TNF-α, and IL-1β release fromHLMs; promoted efficient phagocytosis; and induced dysfunction of intracellular Ca2+ concentrationby increasing lysosomal Ca2+ content in HLMs. Microscopy experiments revealed that HLM trackingwas affected by spike protein activation. Finally, HLMs constitutively expressed mRNAs for ACE2and TMPRSS2. In conclusion, during SARS-CoV-2 infection, macrophages seem to play a key role inlung injury, resulting in immunological dysfunction and respiratory disease.