Dataset Information

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.

SUBMITTER: Reijnders TDY

PROVIDER: S-EPMC10704504 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

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

Reijnders Tom D Y TDY Schuurman Alex R AR Verhoeff Jan J van den Braber Marlous M Douma Renée A RA Faber Daniël R DR Paul Alberta G A AGA Wiersinga W Joost WJ Saris Anno A Garcia Vallejo Juan J JJ van der Poll Tom T

Frontiers in immunology 20231124

<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>We identified 86 immune cell metaclusters, 19 of which (22. ...[more]

PMID: 38077404

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Project description:BackgroundCommunity-acquired pneumonia (CAP) can be caused by a variety of pathogens, of which Streptococcus pneumoniae, Influenza and currently SARS-CoV-2 are the most common. We sought to identify shared and pathogen-specific host response features by directly comparing different aetiologies of CAP.MethodsWe measured 72 plasma biomarkers in a cohort of 265 patients hospitalized for CAP, all sampled within 48 hours of admission, and 28 age-and sex matched non-infectious controls. We stratified the biomarkers into several pathophysiological domains- antiviral response, vascular response and function, coagulation, systemic inflammation, and immune checkpoint markers. We directly compared CAP caused by SARS-CoV-2 (COVID-19, n=39), Streptococcus pneumoniae (CAP-strep, n=27), Influenza (CAP-flu, n=22) and other or unknown pathogens (CAP-other, n=177). We adjusted the comparisons for age, sex and disease severity scores.FindingsBiomarkers reflective of a stronger cell-mediated antiviral response clearly separated COVID-19 from other CAPs (most notably granzyme B). Biomarkers reflecting activation and function of the vasculature showed endothelial barrier integrity was least affected in COVID-19, while glycocalyx degradation and angiogenesis were enhanced relative to other CAPs. Notably, markers of coagulation activation, including D-dimer, were not different between the CAP groups. Ferritin was most increased in COVID-19, while other systemic inflammation biomarkers such as IL-6 and procalcitonin were highest in CAP-strep. Immune checkpoint markers showed distinctive patterns in viral and non-viral CAP, with highly elevated levels of Galectin-9 in COVID-19.InterpretationOur investigation provides insight into shared and distinct pathophysiological mechanisms in different aetiologies of CAP, which may help guide new pathogen-specific therapeutic strategies.FundingThis study was financially supported by the Dutch Research Council, the European Commission and the Netherlands Organization for Health Research and Development.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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