Fig. 6: Proposed model of the innate responses associated with COVID-19 severity.
From: Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2
Our longitudinal study of the innate responses by ex-vivo stimulation of PBMCs from COVID-19 patients, and across distinct disease severities (i.e., mild/asymptomatic versus severe COVID-19 and healthy donors, as reference) highlighted the following proposed model. pDCs from mild/asymptomatic patients and healthy donors (in purple) robustly produce IFN-I/λ upon cell contact with SARS-CoV-2-infected cells (upper panel). As opposed, pDCs from severe patients (in red) produce IFN-I/λ in absence of ex vivo stimulation, but fail to be activated by contact with SARS-CoV-2-infected cells (lower panel). This non-responsive/exhausted state of pDCs in severe COVID-19 patients is associated with an elevated level of pro-inflammatory cytokines (here represented by IL-6, red round symbols) that are most likely produced by the HLA-DR+CD14+ monocytes. As shown on the zoomed view of the contact site (right panel, at the top), the short-range sensing of SARS-CoV-2-infected cells by pDCs requires cell contact mediated by adhesion complexes, identified as αLβ2 integrin and ICAM-1. This triggers TLR7-induced signaling via IRF7 leading to an IFN-I/λ-prioritized response while leaving inactive the NF-κB-mediated signaling.
