The innate immune response stimulated by type-I interferon which is in turn secreted by plasmacytoid dendritic cells (pDC) in the initial phase of the SARS-CoV-2 infection, plays a key role in preventing the progression of COVID-19. A team of researchers (Università e Ospedale San Raffaele of Milan, Policlinico di Tor Vergata, University of Padua, the Associazione Fitness Metabolica (Metabolic Fitness Association) coordinated by the Istituto Superiore di Sanità -ISS (Italian National Institute of Health), has placed under the magnifying glass precisely the mechanism of innate immune response in the pathogenesis of COVID-19 in a study published on Plos Pathogens (link).
“We studied the early interaction between SARS-CoV-2 and the cells of the immune system in an in vitro experimental model based on human peripheral blood cells – explained project leader Eliana Coccia of ISS – and we saw that also in the absence of a productive replication of the virus, it still stimulates a considerable secretion of type-I and III IFNs and of inflammatory cytokines and chemokines (i.e. molecules that act as mediators of the innate immune system and of the inflammatory response), which are known for contributing to the cytokine storm observed in COVID-19. As predicted, the type-I IFN secreted by pDCs, is capable of triggering the antiviral response of infected pulmonary epithelial cells.”
Based on this in vitro evidence, researchers characterized the phenotype of pDCs and the balance of antiviral cytokines and pro-inflammatory cytokines in COVID-19 patients according to the severity of the disease. They then proceeded to observe that the PD-L1 expression on the surface of pDCs, as their frequency in peripheral blood, presents differences according to if the patient is asymptomatic or, on the contrary, has a serious condition. “Asymptomatic subjects – added Nicola Clementi from the Università Vita-Salute San Raffaele – have circulating pDCs that secrete the IFNs, and this perfectly combines with extremely high serum levels of type-I IFN and with the expression of IFN-stimulated antiviral genes. On the contrary, patients hospitalized with severe COVID-19 show a very low frequency of circulating pDCs with an inflammatory phenotype and high serum levels of pro-inflammatory cytokines and chemokines.”
“Our study – the authors conclude – confirms the key protective role of the pDC/type-I IFN axis in COVID-19, a better understanding of which could contribute to developing new pharmacological and/or therapeutic strategies aimed at boosting the pDC response from the earliest phases of the SARS-CoV-2 infection”.
The results obtained in the study were achieved through the close collaboration of the researchers and clinicians as specified below:
Infectious Disease Department, Istituto Superiore di Sanità (Rome)
Eliana M Coccia, Marilena P. Etna, Stefano Fiore, Daniela Ricci, Fabiana Rizzo, Martina Severa, Paola Stefanelli;
Infectious Disease Clinic, Policlinico Tor Vergata (Rome)
Massimo Andreoni, Marco Iannetta, Alessandra Lodi;
Department of Molecular Medicine, University of Padua (Padua)
Luisa Barzon, Alessandro Sinigaglia;
Laboratory of Microbiology and Virology, Università Vita-Salute San Raffaele (Milan)
Massimo Clementi, Nicola Clementi, Elena Criscuolo, Roberta Diotti, Nicasio Mancini;
Associazione Fitness Metabolica (Monterotondo)
Stefano Balducci.
