A bird's eye view on the role of dendritic cells in SARS‐CoV‐2 infection: Perspectives for immune‐based vaccines

Abstract

Coronavirus disease‐19 (COVID‐19) is a complex disorder caused by the pandemic diffusion of a novel coronavirus named SARS‐CoV‐2. Clinical manifestations vary from silent infection to severe pneumonia, disseminated thrombosis, multi‐organ failure, and death. COVID‐19 pathogenesis is still not fully elucidated, while increasing evidence suggests that disease phenotypes are strongly related to the virus‐induced immune system's dysregulation. Indeed, when the virus‐host cross talk is out of control, the occurrence of an aberrant systemic inflammatory reaction, named “cytokine storm,” leads to a detrimental impairment of the adaptive immune response. Dendritic cells (DCs) are the most potent antigen‐presenting cells able to support innate immune and promote adaptive responses. Besides, DCs play a key role in the anti‐viral defense. The aim of this review is to focus on DC involvement in SARS‐CoV‐2 infection to better understand pathogenesis and clinical behavior of COVID‐19 and explore potential implications for immune‐based therapy strategies.

SARS-CoV-2 Spike Protein and Its Receptor Binding Domain Promote a Proinflammatory Activation Profile on Human Dendritic Cells

“…DCs are key components in viral infections, either through type I interferon production and the establishment of the antiviral state, or by directly activating the adaptive cellular immune response [ 4 , 5 ]. Their correct function is critical in the control and clinical evolution of the infection by the severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 [ 6 , 7 ]. This virus is the etiologic agent of COVID-19, the ongoing pandemic currently affecting the global community [ 8 , 9 ].…”

“…In most cases, the immune system can control and resolve SARS-CoV-2 infection, and patients experience no symptoms or mild to moderate illness with prompt recovery. Nevertheless, nearly 1–5% of the population, particularly the eldest, develop serious illness, and in some cases death [ 7 , 12 ]. Morbidity and mortality of COVID-19 are closely linked to a dysregulation of the immune response [ 13 ].…”

Plasma Metabolomic Alterations Induced by COVID-19 Vaccination Reveal Putative Biomarkers Reflecting the Immune Response

“…Ceramide levels in human dendritic cells (DCs) are tightly regulated and their accumulation, due to inhibition of their catabolism, sensitizes DCs to ceramide-induced cell death [ 54 ]. DCs are professional antigen-presenting cells [ 55 , 56 ] and key players in innate and adaptive immune responses against viral infections; as expected, their involvement in development of immune response against SARS-CoV-2 infection is critical [ 57 ]. After vaccination, the mRNA contained in the vaccine enters DCs at the injection site or within lymph nodes and high levels of the viral S protein are produced.…”

Vitamin C triggers NF-κB-driven epigenomic reprogramming and enhanced immunogenic responses of dendritic cells

“…On the other hand, immunotherapy with autologous DCs (DC vaccines) has been extensively investigated, with more than 200 completed clinical trials to date( 18 ). Most efforts have been focused on cancer, but some clinical trials have also been initiated to treat infectious diseases such as COVID19 (NCT04685603, NCT05007496)( 38 ). The use of moDCs differentiated ex vivo from monocytes of the same donor is a common and straightforward approach to generating DC vaccines, given the relatively high abundance of these cells in the human blood.…”