A Novel Single Cell RNA-seq Analysis of Non-Myeloid Circulating Cells in Late Sepsis
| Autor: | Marie Gauthier, Lyle L. Moldawer, Alicia M. Mohr, Xiaoru Dong, Azra Bihorac, Frederick A. Moore, Todd M. Brusko, Rhonda Bacher, Lauren S Kelly, Dina C. Nacionales, Tyler J. Loftus, Philip A. Efron, Ricardo Ungaro, Dijoia B Darden, Michael P. Kladde, Marvin L. Dirain, Jaimar Rincon, Maigan A. Brusko, Brittany P Fenner |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
lymphocytes
Adult Male Endotype Time Factors Myeloid Surviving Sepsis Campaign Immunology Inflammation sepsis Sepsis Transcriptome immune cells Immune system scRNA-seq medicine Humans Immunology and Allergy RNA-Seq Lymphopoiesis Original Research Aged Aged 80 and over business.industry Gene Expression Profiling Bacterial Infections Dendritic Cells RC581-607 Middle Aged medicine.disease chronic critical illness Phenotype medicine.anatomical_structure Mycoses Case-Control Studies Female Immunologic diseases. Allergy Single-Cell Analysis medicine.symptom business |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| Popis: | BackgroundWith the successful implementation of the Surviving Sepsis Campaign guidelines, post-sepsis in-hospital mortality to sepsis continues to decrease. Those who acutely survive surgical sepsis will either rapidly recover or develop a chronic critical illness (CCI). CCI is associated with adverse long-term outcomes and 1-year mortality. Although the pathobiology of CCI remains undefined, emerging evidence suggests a post-sepsis state of pathologic myeloid activation, inducing suboptimal lymphopoiesis and erythropoiesis, as well as downstream leukocyte dysfunction. Our goal was to use single-cell RNA sequencing (scRNA-seq) to perform a detailed transcriptomic analysis of lymphoid-derived leukocytes to better understand the pathology of late sepsis.MethodsA mixture of whole blood myeloid-enriched and Ficoll-enriched peripheral blood mononuclear cells from four late septic patients (post-sepsis day 14-21) and five healthy subjects underwent Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq).ResultsWe identified unique transcriptomic patterns for multiple circulating immune cell subtypes, including B- and CD4+, CD8+, activated CD4+ and activated CD8+ T-lymphocytes, as well as natural killer (NK), NKT, and plasmacytoid dendritic cells in late sepsis patients. Analysis demonstrated that the circulating lymphoid cells maintained a transcriptome reflecting immunosuppression and low-grade inflammation. We also identified transcriptomic differences between patients with bacterial versus fungal sepsis, such as greater expression of cytotoxic genes among CD8+ T-lymphocytes in late bacterial sepsis.ConclusionCirculating non-myeloid cells display a unique transcriptomic pattern late after sepsis. Non-myeloid leukocytes in particular reveal a host endotype of inflammation, immunosuppression, and dysfunction, suggesting a role for precision medicine-guided immunomodulatory therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|