Abstract
Alveolar macrophages are tissue-resident immune cells that protect epithelial cells in the alveoli from invasion by pathogens including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore the interaction between macrophages and SARS-CoV-2 is inevitable. However little is known about the role of macrophages in SARS-CoV-2 infection. Here we generated macrophages from human induced pluripotent stem cells (hiPSCs) to investigate the susceptibility of hiPSC-derived macrophages (iM8) to the authentic SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variants as well as their gene expression profiles of proinflammatory cytokines during infection. With undetectable angiotensin-converting enzyme 2 (ACE2) mRNA and protein expression iM8 were susceptible to productive infection with the Delta variant whereas infection of iM8 with the Omicron variant was abortive. Interestingly Delta induced cell-cell fusion or syncytia formation in iM8 which was not observed in Omicron-infected cells. However iM8 expressed moderate levels of proinflammatory cytokine genes in response to SARS-CoV-2 infection in contrast to strong upregulation of these cytokine genes in response to polarization by lipopolysaccharide (LPS) and interferon-gamma (IFN-? ). Overall our findings indicate that the SARS-CoV-2 Delta variant can replicate and cause syncytia formation in macrophages suggesting that the Delta variant can enter cells with undetectable ACE2 levels and exhibit greater fusogenicity. Copyright 2023 Thaweerattanasinp et al.
