Dendritic Cells and SARS-CoV-2 Infection: Still an Unclarified Connection

Abstract

The ongoing pandemic due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has so far infected about 2.42 × 107 (as at 27 August 2020) subjects with more than 820,000 deaths. It is the third zoonotic coronavirus-dependent outbreak in the last twenty years and represents a major infective threat for public health worldwide. A main aspect of the infection, in analogy to other viral infections, is the so-called “cytokine storm”, an inappropriate molecular response to virus spread which plays major roles in tissue and organ damage. Immunological therapies, including vaccines and humanized monoclonal antibodies, have been proposed as major strategies for prevention and treatment of the disease. Accordingly, a detailed mechanistic knowledge of the molecular events with which the virus infects cells and induces an immunological response appears necessary. In this review, we will report details of the initial process of SARS-CoV-2 cellular entry with major emphasis on the maturation of the spike protein. Then, a particular focus will be devoted to describe the possible mechanisms by which dendritic cells, a major cellular component of innate and adaptive immune responses, may play a role in the spread of the virus in the human body and in the clinical evolution of the disease.

COVID-19 and Cardiovascular Disease

“… 124 Deficient-type I IFN activation may also be due to autoantibodies that neutralize the ligand and/or receptor, 125 but the mechanisms accounting for a potential failure of type I IFN production are unknown. 126 The extent to which the activity of specific cytokines (eg, IL-6, IL-1β, TNF) is a marker or mediator of disease severity and whether these pathways account for cardiovascular impairment is a crucial knowledge gap and may have relevance to cardiovascular resilience in the face of non-COVID critical illnesses.…”

SARS-CoV-2 mediated neuroinflammation and the impact of COVID-19 in neurological disorders

“…The cell subtype specific interactions of DC in response to SARS. While it appears that DCs numbers are reduced in the acute phase, there were increases of mature dendritic cells in broncho-alveolar lavages of COVID-19 patients suggesting that these cells participate in the response to the infection [ 73 , 74 ]. The mechanism by which SARS-CoV-2 infects dendritic cells is unclear.…”

“…One article suggests that entry into the dendritic cells could be through ACE2 receptors, micropinocytosis or dipeptidyl peptidase 4 (DPP4) receptor interaction. Still, much remains unknown about dendritic cell interaction with SARS-CoV-2 [ 74 ].…”

Endothelial Dysfunction and SARS-CoV-2 Infection: Association and Therapeutic Strategies

“…Coronavirus, order Nidovirales, family Coronaviridae, is composed of a helical capsid and a single-stranded RNA genome with a length of 27–32 kb [ 21 , 22 , 23 , 24 ]. This virus family includes four distinct genera, namely α, β, γ, and δ [ 22 , 25 ]. SARS-CoV-2, the causative pathogen of COVID-19, belongs to the β-genus and is considered a zoonotic pathogen that can infect a variety of species, especially birds and mammals [ 5 , 22 , 25 ].…”