Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release

LI Labzin; KY Chew; K Eschke; X Wang; T Esposito; CJ Stocks; J Rae; R Patrick; H Mostafavi; B Hill; TE Yordanov; CL Holley; S Emming; S Fritzlar; FL Mordant; DP Steinfort; K Subbarao; CM Nefzger; AK Lagendijk; EJ Gordon; RG Parton; KR Short; SL Londrigan; K Schroder

Journal article

Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release

LI Labzin, KY Chew, K Eschke, X Wang, T Esposito, CJ Stocks, J Rae, R Patrick, H Mostafavi, B Hill, TE Yordanov, CL Holley, S Emming, S Fritzlar, FL Mordant, DP Steinfort, K Subbarao, CM Nefzger, AK Lagendijk, EJ Gordon Show all

Science Signaling | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2023

DOI: 10.1126/scisignal.abq1366

Abstract

Macrophages are key cellular contributors to the pathogenesis of COVID-19, the disease caused by the virus SARS-CoV-2. The SARS-CoV-2 entry receptor ACE2 is present only on a subset of macrophages at sites of SARS-CoV-2 infection in humans. Here, we investigated whether SARS-CoV-2 can enter macrophages, replicate, and release new viral progeny; whether macrophages need to sense a replicating virus to drive cytokine release; and, if so, whether ACE2 is involved in these mechanisms. We found that SARS-CoV-2 could enter, but did not replicate within, ACE2-deficient human primary macrophages and did not induce proinflammatory cytokine expression. By contrast, ACE2 overexpression in human THP-1–d..

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University of Melbourne Researchers

Francesca Mordant Author

Daniel Steinfort Author

Kanta Subbarao Author

Sarah Londrigan Author

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia

Awarded by National Heart Foundation of Australia

Funding Acknowledgements

This work was supported by National Health and Medical Research Council (NHMRC) of Australia funding, including fellowships (1124612 to L.L., 1177174 to K. Subbarao, 1156489 to R.G.P., and 2009075 to K. Schroder) and grants (2010757 to L.L. and E.J.G., 2013574 to C.M.N., 1140064 and 1150083 to R.G.P., 2007979 to K.R.S., 1184532 to S.L.L., and 2009677 to K. Schroder) and the Doherty Institute COVID-19 Agility Fund to S.L.L., S.F., K. Subbarao, and D.P.S. E.J.G. is funded by the National Heart Foundation of Australia (Future Leader Fellowship 104692) . The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health.