The transcriptional and phenotypic characteristics that define alveolar macrophage subsets in acute hypoxemic respiratory failure

Eric D. Morrell (), Sarah E. Holton, Matthew Lawrance, Marika Orlov, Zoie Franklin, Mallorie A. Mitchem, Hannah DeBerg, Vivian H. Gersuk, Ashley Garay, Elizabeth Barnes, Ted Liu, Ithan D. Peltan, Angela Rogers, Steven Ziegler, Mark M. Wurfel and Carmen Mikacenic ()
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Eric D. Morrell: University of Washington
Sarah E. Holton: University of Washington
Matthew Lawrance: Benaroya Research Institute
Marika Orlov: University of Colorado
Zoie Franklin: Benaroya Research Institute
Mallorie A. Mitchem: Benaroya Research Institute
Hannah DeBerg: Benaroya Research Institute
Vivian H. Gersuk: Benaroya Research Institute
Ashley Garay: University of Washington
Elizabeth Barnes: University of Washington
Ted Liu: University of Washington
Ithan D. Peltan: Intermountain Health
Angela Rogers: Stanford University
Steven Ziegler: Benaroya Research Institute
Mark M. Wurfel: University of Washington
Carmen Mikacenic: Benaroya Research Institute

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract The transcriptional and phenotypic characteristics that define alveolar monocyte and macrophage subsets in acute hypoxemic respiratory failure (AHRF) are poorly understood. Here, we apply CITE-seq (single-cell RNA-sequencing and cell-surface protein quantification) to bronchoalveolar lavage and blood specimens longitudinally collected from participants with AHRF to identify alveolar myeloid subsets, and then validate their identity in an external cohort using flow cytometry. We identify alveolar myeloid subsets with transcriptional profiles that differ from other lung diseases as well as several subsets with similar transcriptional profiles as reported in healthy participants (Metallothionein) or patients with COVID-19 (CD163/LGMN). We use information from CITE-seq to determine cell-surface proteins that distinguish transcriptional subsets (CD14, CD163, CD123, CD71, CD48, CD86 and CD44). In the external cohort, we find a higher proportion of CD163/LGMN alveolar macrophages are associated with mortality in AHRF. We report a parsimonious set of cell-surface proteins that distinguish alveolar myeloid subsets using scalable approaches that can be applied to clinical cohorts.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43223-0

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DOI: 10.1038/s41467-023-43223-0

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