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COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds

Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and COVID-19-associated mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syn...

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Autores principales: Tappe, Beeke, Lauruschkat, Chris D., Strobel, Lea, Pantaleón García, Jezreel, Kurzai, Oliver, Rebhan, Silke, Kraus, Sabrina, Pfeuffer-Jovic, Elena, Bussemer, Lydia, Possler, Lotte, Held, Matthias, Hünniger, Kerstin, Kniemeyer, Olaf, Schäuble, Sascha, Brakhage, Axel A., Panagiotou, Gianni, White, P. Lewis, Einsele, Hermann, Löffler, Jürgen, Wurster, Sebastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9427195/
https://www.ncbi.nlm.nih.gov/pubmed/36052094
http://dx.doi.org/10.3389/fimmu.2022.954985
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author Tappe, Beeke
Lauruschkat, Chris D.
Strobel, Lea
Pantaleón García, Jezreel
Kurzai, Oliver
Rebhan, Silke
Kraus, Sabrina
Pfeuffer-Jovic, Elena
Bussemer, Lydia
Possler, Lotte
Held, Matthias
Hünniger, Kerstin
Kniemeyer, Olaf
Schäuble, Sascha
Brakhage, Axel A.
Panagiotou, Gianni
White, P. Lewis
Einsele, Hermann
Löffler, Jürgen
Wurster, Sebastian
author_facet Tappe, Beeke
Lauruschkat, Chris D.
Strobel, Lea
Pantaleón García, Jezreel
Kurzai, Oliver
Rebhan, Silke
Kraus, Sabrina
Pfeuffer-Jovic, Elena
Bussemer, Lydia
Possler, Lotte
Held, Matthias
Hünniger, Kerstin
Kniemeyer, Olaf
Schäuble, Sascha
Brakhage, Axel A.
Panagiotou, Gianni
White, P. Lewis
Einsele, Hermann
Löffler, Jürgen
Wurster, Sebastian
author_sort Tappe, Beeke
collection PubMed
description Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and COVID-19-associated mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood stimulation assay, we challenged blood from twelve COVID-19 patients with Aspergillus fumigatus and Rhizopus arrhizus antigens and studied the expression of activation, maturation, and exhaustion markers, as well as cytokine secretion. Compared to healthy controls, T-helper cells from COVID-19 patients displayed increased expression levels of the exhaustion marker PD-1 and weakened A. fumigatus- and R. arrhizus-induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, whole blood from COVID-19 patients elicited diminished release of T-cellular (e.g., IFN-γ, IL-2) and innate immune cell-derived (e.g., CXCL9, CXCL10) cytokines in response to A. fumigatus and R. arrhizus antigens. Additionally, samples from COVID-19 patients showed deficient granulocyte activation by mold antigens and reduced fungal killing capacity of neutrophils. These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies to prevent and treat fungal superinfections in COVID-19 patients.
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spelling pubmed-94271952022-08-31 COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds Tappe, Beeke Lauruschkat, Chris D. Strobel, Lea Pantaleón García, Jezreel Kurzai, Oliver Rebhan, Silke Kraus, Sabrina Pfeuffer-Jovic, Elena Bussemer, Lydia Possler, Lotte Held, Matthias Hünniger, Kerstin Kniemeyer, Olaf Schäuble, Sascha Brakhage, Axel A. Panagiotou, Gianni White, P. Lewis Einsele, Hermann Löffler, Jürgen Wurster, Sebastian Front Immunol Immunology Patients suffering from coronavirus disease-2019 (COVID-19) are susceptible to deadly secondary fungal infections such as COVID-19-associated pulmonary aspergillosis and COVID-19-associated mucormycosis. Despite this clinical observation, direct experimental evidence for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-driven alterations of antifungal immunity is scarce. Using an ex-vivo whole blood stimulation assay, we challenged blood from twelve COVID-19 patients with Aspergillus fumigatus and Rhizopus arrhizus antigens and studied the expression of activation, maturation, and exhaustion markers, as well as cytokine secretion. Compared to healthy controls, T-helper cells from COVID-19 patients displayed increased expression levels of the exhaustion marker PD-1 and weakened A. fumigatus- and R. arrhizus-induced activation. While baseline secretion of proinflammatory cytokines was massively elevated, whole blood from COVID-19 patients elicited diminished release of T-cellular (e.g., IFN-γ, IL-2) and innate immune cell-derived (e.g., CXCL9, CXCL10) cytokines in response to A. fumigatus and R. arrhizus antigens. Additionally, samples from COVID-19 patients showed deficient granulocyte activation by mold antigens and reduced fungal killing capacity of neutrophils. These features of weakened anti-mold immune responses were largely decoupled from COVID-19 severity, the time elapsed since diagnosis of COVID-19, and recent corticosteroid uptake, suggesting that impaired anti-mold defense is a common denominator of the underlying SARS-CoV-2 infection. Taken together, these results expand our understanding of the immune predisposition to post-viral mold infections and could inform future studies of immunotherapeutic strategies to prevent and treat fungal superinfections in COVID-19 patients. Frontiers Media S.A. 2022-08-16 /pmc/articles/PMC9427195/ /pubmed/36052094 http://dx.doi.org/10.3389/fimmu.2022.954985 Text en Copyright © 2022 Tappe, Lauruschkat, Strobel, Pantaleón García, Kurzai, Rebhan, Kraus, Pfeuffer-Jovic, Bussemer, Possler, Held, Hünniger, Kniemeyer, Schäuble, Brakhage, Panagiotou, White, Einsele, Löffler and Wurster https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Tappe, Beeke
Lauruschkat, Chris D.
Strobel, Lea
Pantaleón García, Jezreel
Kurzai, Oliver
Rebhan, Silke
Kraus, Sabrina
Pfeuffer-Jovic, Elena
Bussemer, Lydia
Possler, Lotte
Held, Matthias
Hünniger, Kerstin
Kniemeyer, Olaf
Schäuble, Sascha
Brakhage, Axel A.
Panagiotou, Gianni
White, P. Lewis
Einsele, Hermann
Löffler, Jürgen
Wurster, Sebastian
COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
title COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
title_full COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
title_fullStr COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
title_full_unstemmed COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
title_short COVID-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
title_sort covid-19 patients share common, corticosteroid-independent features of impaired host immunity to pathogenic molds
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9427195/
https://www.ncbi.nlm.nih.gov/pubmed/36052094
http://dx.doi.org/10.3389/fimmu.2022.954985
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