A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections

Abstract

Dendritic cells (DC) connect the innate and adaptive arms of the immune system and carry out numerous roles that are significant in the context of viral disease. Their functions include the control of inflammatory responses, the promotion of tolerance, cross-presentation, immune cell recruitment and the production of antiviral cytokines. Based primarily on the available literature that characterizes the behaviour of many DC subsets during Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19), we speculated possible mechanisms through which DC could contribute to COVID-19 immune responses, such as dissemination of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to lymph nodes, mounting dysfunctional inteferon responses and T cell immunity in patients. We highlighted gaps of knowledge in our understanding of DC in COVID-19 pathogenesis and discussed current pre-clinical development of therapies for COVID-19.

Keywords: COVID-19; SARS-CoV2; dendritic cells; immunopathology; therapy.

Figure 1

Potential dendritic cells (DC) Dysfunction(s) in coronavirus disease 2019 (COVID-19) patients. In viral dissemination, DC could be abortively infected by SARS-CoV-2. Infected DC may spread to infect permissive cells through trans-infection, or gain access to the bloodstream for dissemination throughout the body. In innate immunity, moDC infected with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demonstrate antagonized type I IFN production. Reduced type I IFN levels facilitate viral replication at sites of infection. DC maturation has been found to be inhibited in vivo. In Adaptive immunity, compromised DC maturation could impair naïve T-cell primings and may indirectly contribute to observed T cell lymphopenias, which collectively can impair viral clearance. As diverse DC subsets have specific functional activities, DC subsets may also induce different functional responses to SARS-CoV-2 infection in vivo.