COVID-19 severity associates with pulmonary redistribution of CD1c+ DCs and inflammatory transitional and nonclassical monocytes
Ildefonso Sánchez-Cerrillo, … , Enrique Martín-Gayo, the REINMUN-COVID and EDEPIMIC groups
Ildefonso Sánchez-Cerrillo, … , Enrique Martín-Gayo, the REINMUN-COVID and EDEPIMIC groups
Published August 12, 2020
Citation Information: J Clin Invest. 2020;130(12):6290-6300. https://doi.org/10.1172/JCI140335.
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Research Article COVID-19 Immunology

COVID-19 severity associates with pulmonary redistribution of CD1c+ DCs and inflammatory transitional and nonclassical monocytes

Abstract

SARS-CoV-2 is responsible for the development of coronavirus disease 2019 (COVID-19) in infected individuals, who can either exhibit mild symptoms or progress toward a life-threatening acute respiratory distress syndrome (ARDS). 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. Here, we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood and lung of COVID-19 patients with different clinical severity in comparison with healthy 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. Our results indicate that inflammatory transitional and nonclassical monocytes and CD1c+ conventional dendritic cells preferentially migrate from blood to lungs in patients with severe COVID-19. Thus, this study increases the knowledge of specific myeloid subsets involved in the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies for fighting SARS-CoV-2 infection.

Authors

Ildefonso Sánchez-Cerrillo, Pedro Landete, Beatriz Aldave, Santiago Sánchez-Alonso, Ana Sánchez-Azofra, Ana Marcos-Jiménez, Elena Ávalos, Ana Alcaraz-Serna, Ignacio de los Santos, Tamara Mateu-Albero, Laura Esparcia, Celia López-Sanz, Pedro Martínez-Fleta, Ligia Gabrie, Luciana del Campo Guerola, Hortensia de la Fuente, María J. Calzada, Isidoro González-Álvaro, Arantzazu Alfranca, Francisco Sánchez-Madrid, Cecilia Muñoz-Calleja, Joan B. Soriano, Julio Ancochea, Enrique Martín-Gayo, the REINMUN-COVID and EDEPIMIC groups

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Figure 6

Association between effector CD8+ T cell and inflammatory myeloid cells present in bronchoscopy from COVID-19 patients with ARDS.

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Association between effector CD8+ T cell and inflammatory myeloid cells ...
(A) Representative flow cytometry analysis of CD38 versus CXCR5 expression on gated CD8+ T cells present in the blood (left) and paired bronchoscopy infiltrate (right) from COVID-19 patients with ARDS. Numbers on quadrants represent percentages of positive cells. (B) Box-and-whiskers plots representing analysis of frequencies of CXCR5+CD38+ (left), CXCR5+CD38– (center), and CXCR5–CD38+ (right) CD8+ T cells present in paired blood and bronchoscopy samples from n = 15 COVID-19 patients presenting with ARDS. Frequencies of these CD8+ T cell subsets on the blood of n = 17 non–COVID-19 controls were included for reference. Error bars represent maximum and minimum values. Statistical significance of differences in frequencies between paired blood vs. bronchoscopy samples (blue) or comparison with healthy controls (black) was calculated using a 2-tailed matched pairs Wilcoxon’s and Mann-Whitney U test with Bonferroni’s multiple comparison correction, respectively. *P < 0.05; **P < 0.01; ***P < 0.001. (C) Spearman’s and Pearson’s correlations between proportions of the indicated effector CD8+ T cells subset and CD40 MFI on T Mo. Spearman’s and Pearson’s P and R values are shown in the upper right corner on each correlation plot.