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. 2022 May 7;43(6):417–419. doi: 10.1016/j.it.2022.04.007

Figure 1.

Figure 1

Fc-receptor mediated uptake of IgG-opsonized SARS-CoV-2 triggers pyroptosis in monocytes.

(Anticlockwise) ① SARS-CoV-2-specific antibodies (IgG) elicited by infection or vaccination can opsonize SARS-CoV-2 virions. ② Opsonized SARS-CoV-2 virions then bind to Fc receptors CD16 and/or CD64 on monocytes, triggering internalization ③. This leads to infection of monocytes ④ and viral replication ⑤. However, active infections within monocytes are abruptly terminated because activated inflammasomes in turn activate caspase-1, leading to gasdermin (GSDMD) cleavage ⑥. Cleaved N-terminal GSDMD translocates to the plasma membrane where it assembles into pores ⑦. This causes the infected monocytes to undergo pyroptosis and rupture instead, releasing mature, active proinflammatory cytokines such as IL-18 and IL-1β into the milieu ⑧. This in turn could recruit more immune cells to the site, perpetuating the inflammatory cascade and leading to a cytokine storm [5]. Steps which remain unclear after the current study [5] and warrant further research are indicated in red. Abbreviation: SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Figure created with BioRender.com.