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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 Immunology Article has an altmetric score of 66

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

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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 5

Characterization of myeloid cell subsets present in bronchoscopy infiltrates from COVID-19 patients with ARDS.

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Characterization of myeloid cell subsets present in bronchoscopy infiltr...
(A) Box-and-whiskers plots showing percentages of the indicated cell populations in the hematopoietic CD45+ infiltrate present in bronchoscopy mucus samples from severe COVID-19 patients (n = 23) presenting ARDS and receiving IMV at ICU. Error bars represent maximum and minim values. Statistical differences between proportions of cell populations within the same infiltrates were calculated using Friedman’s test for multiple comparisons. *P < 0.05; **P < 0.01; ****P < 0.0001. (B and C) Frequencies (B) and CD40 MFI (C) of CD1c+ and CD141+ cDCs (left) and T and NC Mo (right) in paired blood and bronchoscopy samples from COVID-19 patients presenting with ARDS (n = 15). Statistical significance of differences in frequencies between paired blood vs. bronchoscopy samples (black) or between different cell subsets within either blood (blue) or bronchoscopy infiltrates (pink) was calculated using a 2-tailed matched pairs Wilcoxon’s test. *P < 0.05; **P < 0.01; ***P < 0.001. (D) Box-and-whiskers plots representing comparison of CD40 MFI on the indicated myeloid cell populations present in the bronchoscopy infiltrates of total critical G3 COVID-19 patients. Error bars represent maximum and minimum values. Statistical significance of differences was calculated using Friedman’s test for multiple comparisons. *P < 0.05; **P < 0.01; ****P < 0.0001. (E) Spearman’s correlations between CRP levels in plasma and CD40 MFI on NC Mo present in the bronchoscopy infiltrates of severe COVID-19 patients. Spearman’s P and R values are shown in the upper right corner of the plot.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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