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The Transcriptional and Phenotypic Characteristics that Define Alveolar Macrophage Subsets in Acute Hypoxemic Respiratory Failure

ABSTRACT: The transcriptional and phenotypic characteristics that define alveolar monocyte and macrophage subsets in acute hypoxemic respiratory failure (AHRF) are poorly understood. We applied CITE-seq (single-cell RNA-sequencing + cell-surface protein quantification) to bronchoalveolar lavage fluid and peripheral blood cells longitudinally collected from subjects with AHRF to identify novel alveolar monocyte/macrophage subsets, and then validated their identity in an external cohort using flow cytometry. We identified 2 monocyte and 6 macrophage subsets in alveolar samples using CITE-seq data. Some of the subsets had similar transcriptional profiles as those reported in healthy subjects (metallothionein genes) or patients with COVID-19 (LGMN-expressing). We also identified novel subsets with transcriptional signatures that straddled previously reported monocyte and macrophage subsets. We used 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 found a higher proportion of CD163/LGMN alveolar macrophages was associated with mortality. We report a parsimonious set of cell-surface proteins that can distinguish alveolar monocyte/macrophage subsets using scalable approaches that can be applied to clinical cohorts.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234918 | GEO | 2023/10/10

REPOSITORIES: GEO

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