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

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

doi:https://doi.org/10.3389/fimmu.2023.1260283

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

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

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background: Community-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. Methods: We 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). Results: We 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. Conclusion: CAP 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.

Original language	English
Article number	1260283
Journal	Frontiers in immunology
Volume	14
DOIs	https://doi.org/10.3389/fimmu.2023.1260283
Publication status	Published - 2023

Keywords

COVID-19
chemokine receptors
host response
immunophenotyping
immunosuppression
monocytes
pneumonia
spectral flow cytometry

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Reijnders, T. D. Y., Schuurman, A. R., Verhoeff, J., van den Braber, M., Douma, R. A., Faber, D. R., Paul, A. G. A., Wiersinga, W. J., Saris, A., Garcia Vallejo, J. J., & van der Poll, T. (2023). High-dimensional phenotyping of the peripheral immune response in community-acquired pneumonia. Frontiers in immunology, 14, Article 1260283. https://doi.org/10.3389/fimmu.2023.1260283

@article{23844e9979224fa09fb90359296155f2,

title = "High-dimensional phenotyping of the peripheral immune response in community-acquired pneumonia",

abstract = "Background: Community-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. Methods: We 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). Results: We 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. Conclusion: CAP 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.",

keywords = "COVID-19, chemokine receptors, host response, immunophenotyping, immunosuppression, monocytes, pneumonia, spectral flow cytometry",

author = "Reijnders, {Tom D. Y.} and Schuurman, {Alex R.} and Jan Verhoeff and {van den Braber}, Marlous and Douma, {Ren{\'e}e A.} and Faber, {Dani{\"e}l R.} and Paul, {Alberta G. A.} and Wiersinga, {W. Joost} and Anno Saris and {Garcia Vallejo}, {Juan J.} and {van der Poll}, Tom",

note = "Funding Information: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. TR is supported by research program “NACTAR,” project “MDR-phage” (grant number 16447) which is financed by the Dutch research council (NWO). TP is supported by grants from the Innovative Medicines Initiative (IMI) and the European Union (COMBACTE-CARE and COMBACTE-MAGNET). Acknowledgments Publisher Copyright: Copyright {\textcopyright} 2023 Reijnders, Schuurman, Verhoeff, van den Braber, Douma, Faber, Paul, Wiersinga, Saris, Garcia Vallejo and van der Poll.",

year = "2023",

doi = "https://doi.org/10.3389/fimmu.2023.1260283",

language = "English",

volume = "14",

journal = "Frontiers in immunology",

issn = "1664-3224",

publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - High-dimensional phenotyping of the peripheral immune response in community-acquired pneumonia

AU - Reijnders, Tom D. Y.

AU - Schuurman, Alex R.

AU - Verhoeff, Jan

AU - van den Braber, Marlous

AU - Douma, Renée A.

AU - Faber, Daniël R.

AU - Paul, Alberta G. A.

AU - Wiersinga, W. Joost

AU - Saris, Anno

AU - Garcia Vallejo, Juan J.

AU - van der Poll, Tom

N1 - Funding Information: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. TR is supported by research program “NACTAR,” project “MDR-phage” (grant number 16447) which is financed by the Dutch research council (NWO). TP is supported by grants from the Innovative Medicines Initiative (IMI) and the European Union (COMBACTE-CARE and COMBACTE-MAGNET). Acknowledgments Publisher Copyright: Copyright © 2023 Reijnders, Schuurman, Verhoeff, van den Braber, Douma, Faber, Paul, Wiersinga, Saris, Garcia Vallejo and van der Poll.

PY - 2023

Y1 - 2023

N2 - Background: Community-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. Methods: We 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). Results: We 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. Conclusion: CAP 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.

AB - Background: Community-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. Methods: We 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). Results: We 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. Conclusion: CAP 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.

KW - COVID-19

KW - chemokine receptors

KW - host response

KW - immunophenotyping

KW - immunosuppression

KW - monocytes

KW - pneumonia

KW - spectral flow cytometry

UR - http://www.scopus.com/inward/record.url?scp=85178915890&partnerID=8YFLogxK

U2 - https://doi.org/10.3389/fimmu.2023.1260283

DO - https://doi.org/10.3389/fimmu.2023.1260283

M3 - Article

C2 - 38077404

SN - 1664-3224

VL - 14

JO - Frontiers in immunology

JF - Frontiers in immunology

M1 - 1260283

ER -

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

Abstract

Keywords

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