Differential Redistribution of Activated Monocyte and Dendritic Cell Subsets to the Lung Associates with Severity of COVID-19

Sanchez-Cerrillo, I.; Landete, P.; Aldave, B.; Sanchez-Alonso, S.; Sanchez-Azofra, A.; Marcos-Jimenez, A.; Avalos, E.; Alcaraz-Serna, A.; de los Santos, I.; Mateu-Albero, T.; Esparcia, L.; Lopez-Sanz, C.; Martinez-Fleta, P.; Gabrie, L.; del Campo Guerola, L.; Calzada, M. J.; Gonzalez-Alvaro, I.; Alfranca, A.; Sanchez-Madrid, F.; Munoz-Calleja, C.; Soriano, J. B.; Ancochea, J.; Martin-Gayo, E.

The SARS-CoV-2 is responsible for the pandemic COVID-19 in infected individuals, who can either exhibit mild symptoms or progress towards a life-threatening acute respiratory distress syndrome (ARDS). It is known that exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. With the aim to improve the knowledge in this area, we developed a cross-sectional study, in which we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood of COVID-19 patients with different clinical severity in comparison with healthy control individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Collectively, our results suggest that inflammatory transitional and non-classical monocytes preferentially migrate from blood to lungs in patients with severe COVID-19. CD1c+ conventional dendritic cells also followed this pattern, whereas CD141+ conventional and CD123hi plasmacytoid dendritic cells were depleted from blood but were absent in the lungs. Thus, this study increases the knowledge on the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies to fight SARS-CoV-2 infection.