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
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	dendritic cells maturation homing SARS-CoV-2 COVID-19 diffuse alveolar damage (DAD) Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/5e2ed39ce4a14ab0b3c8204ee0e61fc3
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id	oai: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 AT tinaschaller impaireddendriticcellhomingincovid19 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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Impaired Dendritic Cell Homing in COVID-19

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