Abstract
Dendritic cells (DCs) are the most potent antigen-presenting cells, and their function is essential to configure adaptative immunity and avoid excessive inflammation. DCs are predicted to play a crucial role in the clinical evolution of the infection by the severe acute respiratory syndrome (SARS) coronavirus (CoV)-2. DCs interaction with the SARS-CoV-2 Spike protein, which mediates cell receptor binding and subsequent fusion of the viral particle with host cell, is a key step to induce effective immunity against this virus and in the S protein-based vaccination protocols. Here we evaluated human DCs in response to SARS-CoV-2 S protein, or to a fragment encompassing the receptor binding domain (RBD) challenge. Both proteins increased the expression of maturation markers, including MHC molecules and costimulatory receptors. DCs interaction with the SARS-CoV-2 S protein promotes activation of key signaling molecules involved in inflammation, including MAPK, AKT, STAT1, and NFκB, which correlates with the expression and secretion of distinctive proinflammatory cytokines. Differences in the expression of ACE2 along the differentiation of human monocytes to mature DCs and inter-donor were found. Our results show that SARS-CoV-2 S protein promotes inflammatory response and provides molecular links between individual variations and the degree of response against this virus.
Highlights
Dendritic cells (DCs) are bone-marrow-derived cells distributed at the main entry sites of pathogens as immature dendritic cells
When immature dendritic cells (iDCs) recognize antigens, they turn on a maturation program characterized by cytokine secretion, as well as expression of surface molecules that led to the acquisition of migratory and costimulatory capacities
To investigate how human DCs respond against the S protein of SARSCoV-2, we differentiated primary DCs from monocytes of healthy donors and challenged them with either complete S protein or with the region that contains the receptor binding domain (RBD) region
Summary
Dendritic cells (DCs) are bone-marrow-derived cells distributed at the main entry sites of pathogens as immature dendritic cells (iDCs). These antigen-presenting cells (APCs) express a vast arsenal of pattern recognition receptors (PRRs), through which they sense a broad range of pathogens-associated molecular patterns (PAMPs) for its capture and processing [1]. Mature dendritic cells (mDCs) reach the lymph node and present the processed antigens to naïve T cells at the immune synapse (IS) context. DCs essential activity must be tightly regulated to achieve an effective T cell response while avoiding exacerbating inflammation. Deepening into the mechanisms of immune system activation and regulation by DCs will provide valuable tools for counteracting pathogens and designing effective vaccines
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