Abstract
The exact role of innate immune cells upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and their contribution to the formation of the corona virus-induced disease (COVID)-19 associated cytokine storm is not yet fully understood. We show that human in vitro differentiated myeloid dendritic cells (mDC) as well as M1 and M2 macrophages are susceptible to infection with SARS-CoV-2 but are not productively infected. Furthermore, infected mDC, M1-, and M2 macrophages show only slight changes in their activation status. Surprisingly, none of the infected innate immune cells produced the pro-inflammatory cytokines interleukin (IL)−6, tumor necrosis factor (TNF)-α, or interferon (IFN)−α. Moreover, even in co-infection experiments using different stimuli, as well as non-influenza (non-flu) or influenza A (flu) viruses, only very minor IL-6 production was induced. In summary, we conclude that mDC and macrophages are unlikely the source of the first wave of cytokines upon infection with SARS-CoV-2.
Highlights
In December 2019, a novel coronavirus, later named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused an outbreak of respiratory illness in Wuhan, China [1,2,3]
In order to investigate the viability of innate immune cells upon infection with SARS-CoV-2, we infected in vitro differentiated myeloid dendritic cells (mDC) as well as M1, and M2 macrophages using a multiplicity of infection (MOI) of 0.01 and 0.1 for the indicated time points
No newly formed viral particles were detected within the SN of mDC, M1, or M2 macrophages 24 or 48 h post infection (Figure 1D) indicating that the cells are infected without producing progeny
Summary
In December 2019, a novel coronavirus, later named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused an outbreak of respiratory illness in Wuhan, China [1,2,3]. Severe infections can rapidly progress to pneumonia and result in coronavirus disease (COVID-19) [4]. As of April 29, 2021, data from Johns Hopkins University indicate over one Abbreviations: ACE2, Angiotensin-converting enzyme 2; AT2, type II alveolar epithelial cells; COVID-19, corona virusinduced disease; DC, dendritic cells; DRK, Deutsches Rotes Kreuz; ELISA, enzyme-linked immunosorbent assay; flu, influenza A; h, hours; hpi, hours post infection; IFN-a, interferon alpha; IL, interleukin; MCP-, monocyte chemoattractant protein 1; MERS, Middle East Respiratory Syndrome; MOI, multiplicity of infection; PRRSV, Porcine reproductive and respiratory syndrome virus; RVFV, Rift Valley Fever virus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SeV, Sendai virus; SN, supernatants; TLR, Toll-like receptor; TNF-a; tumor necrosis factor alpha; VSV, Vesicular stomatitis virus Indiana. Other studies predicted an interaction of SARS-CoV-2 spike protein with CD147 and CD26, which are expressed on innate immune cells [9,10,11]
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