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:10.3389/fimmu.2023.1260283

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

Front Immunol. 2023 Nov 24:14:1260283. doi: 10.3389/fimmu.2023.1260283. eCollection 2023.

Authors

Affiliations

¹ Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC location University of Amsterdam, Amsterdam, Netherlands.
² Department of Molecular Cell Biology and Immunology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
³ Department of Internal Medicine, Flevo Hospital, Almere, Netherlands.
⁴ Department of Internal Medicine, BovenIJ Hospital, Amsterdam, Netherlands.
⁵ Application Department, Cytek Biosciences, Inc., Fremont, CA, United States.
⁶ Division of Infectious Diseases, Amsterdam UMC location University of Amsterdam, Amsterdam, Netherlands.
⁷ Infectious Disease, Leiden Universitair Medisch Centrum, Leiden, Netherlands.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
COVID-19*
Community-Acquired Infections*
Humans
Immunity
Leukocytes, Mononuclear
Pneumonia*
Receptors, CCR7

Substances

Receptors, CCR7

Grants and funding

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).