High-dimensional phenotyping of the peripheral immune response in community-acquired pneumonia

BackgroundCommunity-acquired pneumonia (CAP) represents a major health burden worldwide. Dysregulation of the immune response plays an important role in adverse outcomes in patients with CAP.MethodsWe analyzed peripheral blood mononuclear cells by 36-color spectral flow cytometry in adult patients h...

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Main Authors: Tom D. Y. Reijnders, Alex R. Schuurman, Jan Verhoeff, Marlous van den Braber, Renée A. Douma, Daniël R. Faber, Alberta G. A. Paul, W. Joost Wiersinga, Anno Saris, Juan J. Garcia Vallejo, Tom van der Poll
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-11-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1260283/full
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author Tom D. Y. Reijnders
Alex R. Schuurman
Jan Verhoeff
Marlous van den Braber
Renée A. Douma
Daniël R. Faber
Alberta G. A. Paul
W. Joost Wiersinga
W. Joost Wiersinga
Anno Saris
Juan J. Garcia Vallejo
Tom van der Poll
Tom van der Poll
author_facet Tom D. Y. Reijnders
Alex R. Schuurman
Jan Verhoeff
Marlous van den Braber
Renée A. Douma
Daniël R. Faber
Alberta G. A. Paul
W. Joost Wiersinga
W. Joost Wiersinga
Anno Saris
Juan J. Garcia Vallejo
Tom van der Poll
Tom van der Poll
author_sort Tom D. Y. Reijnders
collection DOAJ
description BackgroundCommunity-acquired pneumonia (CAP) represents a major health burden worldwide. Dysregulation of the immune response plays an important role in adverse outcomes in patients with CAP.MethodsWe analyzed peripheral blood mononuclear cells by 36-color spectral flow cytometry in adult patients hospitalized for CAP (n=40), matched control subjects (n=31), and patients hospitalized for COVID-19 (n=35).ResultsWe identified 86 immune cell metaclusters, 19 of which (22.1%) were differentially abundant in patients with CAP versus matched controls. The most notable differences involved classical monocyte metaclusters, which were more abundant in CAP and displayed phenotypic alterations reminiscent of immunosuppression, increased susceptibility to apoptosis, and enhanced expression of chemokine receptors. Expression profiles on classical monocytes, driven by CCR7 and CXCR5, divided patients with CAP into two clusters with a distinct inflammatory response and disease course. The peripheral immune response in patients with CAP was highly similar to that in patients with COVID-19, but increased CCR7 expression on classical monocytes was only present in CAP.ConclusionCAP is associated with profound cellular changes in blood that mainly relate to classical monocytes and largely overlap with the immune response detected in COVID-19.
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spelling doaj.art-1c395277784f45d4a2292698566e39b72023-11-24T10:31:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-11-011410.3389/fimmu.2023.12602831260283High-dimensional phenotyping of the peripheral immune response in community-acquired pneumoniaTom D. Y. Reijnders0Alex R. Schuurman1Jan Verhoeff2Marlous van den Braber3Renée A. Douma4Daniël R. Faber5Alberta G. A. Paul6W. Joost Wiersinga7W. Joost Wiersinga8Anno Saris9Juan J. Garcia Vallejo10Tom van der Poll11Tom van der Poll12Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC location University of Amsterdam, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine (CEMM), Amsterdam UMC location University of Amsterdam, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, NetherlandsDepartment of Internal Medicine, Flevo Hospital, Almere, NetherlandsDepartment of Internal Medicine, BovenIJ Hospital, Amsterdam, NetherlandsApplication Department, Cytek Biosciences, Inc., Fremont, CA, United StatesCenter for Experimental and Molecular Medicine (CEMM), Amsterdam UMC location University of Amsterdam, Amsterdam, NetherlandsDivision of Infectious Diseases, Amsterdam UMC location University of Amsterdam, Amsterdam, NetherlandsInfectious Disease, Leiden Universitair Medisch Centrum, Leiden, NetherlandsDepartment of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, NetherlandsCenter for Experimental and Molecular Medicine (CEMM), Amsterdam UMC location University of Amsterdam, Amsterdam, NetherlandsDivision of Infectious Diseases, Amsterdam UMC location University of Amsterdam, Amsterdam, NetherlandsBackgroundCommunity-acquired pneumonia (CAP) represents a major health burden worldwide. Dysregulation of the immune response plays an important role in adverse outcomes in patients with CAP.MethodsWe analyzed peripheral blood mononuclear cells by 36-color spectral flow cytometry in adult patients hospitalized for CAP (n=40), matched control subjects (n=31), and patients hospitalized for COVID-19 (n=35).ResultsWe identified 86 immune cell metaclusters, 19 of which (22.1%) were differentially abundant in patients with CAP versus matched controls. The most notable differences involved classical monocyte metaclusters, which were more abundant in CAP and displayed phenotypic alterations reminiscent of immunosuppression, increased susceptibility to apoptosis, and enhanced expression of chemokine receptors. Expression profiles on classical monocytes, driven by CCR7 and CXCR5, divided patients with CAP into two clusters with a distinct inflammatory response and disease course. The peripheral immune response in patients with CAP was highly similar to that in patients with COVID-19, but increased CCR7 expression on classical monocytes was only present in CAP.ConclusionCAP is associated with profound cellular changes in blood that mainly relate to classical monocytes and largely overlap with the immune response detected in COVID-19.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1260283/fullpneumoniaimmunophenotypinghost responseCOVID-19spectral flow cytometrymonocytes
spellingShingle Tom D. Y. Reijnders
Alex R. Schuurman
Jan Verhoeff
Marlous van den Braber
Renée A. Douma
Daniël R. Faber
Alberta G. A. Paul
W. Joost Wiersinga
W. Joost Wiersinga
Anno Saris
Juan J. Garcia Vallejo
Tom van der Poll
Tom van der Poll
High-dimensional phenotyping of the peripheral immune response in community-acquired pneumonia
Frontiers in Immunology
pneumonia
immunophenotyping
host response
COVID-19
spectral flow cytometry
monocytes
title High-dimensional phenotyping of the peripheral immune response in community-acquired pneumonia
title_full High-dimensional phenotyping of the peripheral immune response in community-acquired pneumonia
title_fullStr High-dimensional phenotyping of the peripheral immune response in community-acquired pneumonia
title_full_unstemmed High-dimensional phenotyping of the peripheral immune response in community-acquired pneumonia
title_short High-dimensional phenotyping of the peripheral immune response in community-acquired pneumonia
title_sort high dimensional phenotyping of the peripheral immune response in community acquired pneumonia
topic pneumonia
immunophenotyping
host response
COVID-19
spectral flow cytometry
monocytes
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1260283/full
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