Impaired Dendritic Cell Homing in COVID-19

The high mortality of COVID-19 is mostly attributed to acute respiratory distress syndrome (ARDS), whose histopathological correlate is diffuse alveolar damage (DAD). Furthermore, severe COVID-19 is often accompanied by a cytokine storm and a disrupted response of the adaptive immune system. Studies...

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Autores principales: Lukas Borcherding, Alime Sema Teksen, Bianca Grosser, Tina Schaller, Klaus Hirschbühl, Rainer Claus, Oliver Spring, Michael Wittmann, Christoph Römmele, Éva Sipos, Bruno Märkl
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/5e2ed39ce4a14ab0b3c8204ee0e61fc3
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spelling oai:doaj.org-article:5e2ed39ce4a14ab0b3c8204ee0e61fc32021-11-04T05:26:02ZImpaired Dendritic Cell Homing in COVID-192296-858X10.3389/fmed.2021.761372https://doaj.org/article/5e2ed39ce4a14ab0b3c8204ee0e61fc32021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.761372/fullhttps://doaj.org/toc/2296-858XThe high mortality of COVID-19 is mostly attributed to acute respiratory distress syndrome (ARDS), whose histopathological correlate is diffuse alveolar damage (DAD). Furthermore, severe COVID-19 is often accompanied by a cytokine storm and a disrupted response of the adaptive immune system. Studies aiming to depict this dysregulation have mostly investigated the peripheral cell count as well as the functionality of immune cells. We investigated the impact of SARS-CoV-2 on antigen-presenting cells using multiplexed immunofluorescence. Similar to MERS-CoV and SARS-CoV, SARS-CoV-2 appears to be impairing the maturation of dendritic cells (DCs). DC maturation involves a switch in surface antigen expression, which enables the cells' homing to lymph nodes and the subsequent activation of T-cells. As quantitative descriptions of the local inflammatory infiltrate are still scarce, we compared the cell population of professional antigen-presenting cells (APC) in the lungs of COVID-19 autopsy cases in different stages of DAD. We found an increased count of myeloid dendritic cells (mDCs) in later stages. Interestingly, mDCs also showed no significant upregulation of maturation markers in DAD-specimens with high viral load. Accumulation of immature mDCs, which are unable to home to lymph nodes, ultimately results in an inadequate T-cell response.Lukas BorcherdingAlime Sema TeksenBianca GrosserTina SchallerKlaus HirschbühlRainer ClausOliver SpringMichael WittmannChristoph RömmeleÉva SiposBruno MärklFrontiers Media S.A.articledendritic cellsmaturationhomingSARS-CoV-2COVID-19diffuse alveolar damage (DAD)Medicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021)
institution DOAJ
collection DOAJ
language EN
topic dendritic cells
maturation
homing
SARS-CoV-2
COVID-19
diffuse alveolar damage (DAD)
Medicine (General)
R5-920
spellingShingle dendritic cells
maturation
homing
SARS-CoV-2
COVID-19
diffuse alveolar damage (DAD)
Medicine (General)
R5-920
Lukas Borcherding
Alime Sema Teksen
Bianca Grosser
Tina Schaller
Klaus Hirschbühl
Rainer Claus
Oliver Spring
Michael Wittmann
Christoph Römmele
Éva Sipos
Bruno Märkl
Impaired Dendritic Cell Homing in COVID-19
description The high mortality of COVID-19 is mostly attributed to acute respiratory distress syndrome (ARDS), whose histopathological correlate is diffuse alveolar damage (DAD). Furthermore, severe COVID-19 is often accompanied by a cytokine storm and a disrupted response of the adaptive immune system. Studies aiming to depict this dysregulation have mostly investigated the peripheral cell count as well as the functionality of immune cells. We investigated the impact of SARS-CoV-2 on antigen-presenting cells using multiplexed immunofluorescence. Similar to MERS-CoV and SARS-CoV, SARS-CoV-2 appears to be impairing the maturation of dendritic cells (DCs). DC maturation involves a switch in surface antigen expression, which enables the cells' homing to lymph nodes and the subsequent activation of T-cells. As quantitative descriptions of the local inflammatory infiltrate are still scarce, we compared the cell population of professional antigen-presenting cells (APC) in the lungs of COVID-19 autopsy cases in different stages of DAD. We found an increased count of myeloid dendritic cells (mDCs) in later stages. Interestingly, mDCs also showed no significant upregulation of maturation markers in DAD-specimens with high viral load. Accumulation of immature mDCs, which are unable to home to lymph nodes, ultimately results in an inadequate T-cell response.
format article
author Lukas Borcherding
Alime Sema Teksen
Bianca Grosser
Tina Schaller
Klaus Hirschbühl
Rainer Claus
Oliver Spring
Michael Wittmann
Christoph Römmele
Éva Sipos
Bruno Märkl
author_facet Lukas Borcherding
Alime Sema Teksen
Bianca Grosser
Tina Schaller
Klaus Hirschbühl
Rainer Claus
Oliver Spring
Michael Wittmann
Christoph Römmele
Éva Sipos
Bruno Märkl
author_sort Lukas Borcherding
title Impaired Dendritic Cell Homing in COVID-19
title_short Impaired Dendritic Cell Homing in COVID-19
title_full Impaired Dendritic Cell Homing in COVID-19
title_fullStr Impaired Dendritic Cell Homing in COVID-19
title_full_unstemmed Impaired Dendritic Cell Homing in COVID-19
title_sort impaired dendritic cell homing in covid-19
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/5e2ed39ce4a14ab0b3c8204ee0e61fc3
work_keys_str_mv AT lukasborcherding impaireddendriticcellhomingincovid19
AT alimesemateksen impaireddendriticcellhomingincovid19
AT biancagrosser impaireddendriticcellhomingincovid19
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AT klaushirschbuhl impaireddendriticcellhomingincovid19
AT rainerclaus impaireddendriticcellhomingincovid19
AT oliverspring impaireddendriticcellhomingincovid19
AT michaelwittmann impaireddendriticcellhomingincovid19
AT christophrommele impaireddendriticcellhomingincovid19
AT evasipos impaireddendriticcellhomingincovid19
AT brunomarkl impaireddendriticcellhomingincovid19
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