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Nat Med DOI:10.1038/s41591-020-0752-4

An immune-cell signature of bacterial sepsis.

Publication TypeJournal Article
Year of Publication2020
AuthorsReyes, M, Filbin, MR, Bhattacharyya, RP, Billman, K, Eisenhaure, T, Hung, DT, Levy, BD, Baron, RM, Blainey, PC, Goldberg, MB, Hacohen, N
JournalNat Med
Date Published2020 Feb 17
ISSN1546-170X
Abstract

Dysregulation of the immune response to bacterial infection can lead to sepsis, a condition with high mortality. Multiple whole-blood gene-expression studies have defined sepsis-associated molecular signatures, but have not resolved changes in transcriptional states of specific cell types. Here, we used single-cell RNA-sequencing to profile the blood of people with sepsis (n = 29) across three clinical cohorts with corresponding controls (n = 36). We profiled total peripheral blood mononuclear cells (PBMCs, 106,545 cells) and dendritic cells (19,806 cells) across all subjects and, on the basis of clustering of their gene-expression profiles, defined 16 immune-cell states. We identified a unique CD14 monocyte state that is expanded in people with sepsis and validated its power in distinguishing these individuals from controls using public transcriptomic data from subjects with different disease etiologies and from multiple geographic locations (18 cohorts, n = 1,467 subjects). We identified a panel of surface markers for isolation and quantification of the monocyte state and characterized its epigenomic and functional phenotypes, and propose a model for its induction from human bone marrow. This study demonstrates the utility of single-cell genomics in discovering disease-associated cytologic signatures and provides insight into the cellular basis of immune dysregulation in bacterial sepsis.

DOI10.1038/s41591-020-0752-4
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/32066974?dopt=Abstract

Alternate JournalNat. Med.
PubMed ID32066974
Grant ListU24AI118668 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
U24AI118668 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
1K08AI119157-04 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
1DSEP160030-01-00 / / U.S. Department of Health & Human Services | Biomedical Advanced Research and Development Authority (BARDA) /