Details

Autor(en) / Beteiligte

• Darden, Dijoia B
• Dong, Xiaoru
• Brusko, Maigan A
• Kelly, Lauren
• Fenner, Brittany
• Rincon, Jaimar C
• Dirain, Marvin L
• Ungaro, Ricardo
• Nacionales, Dina C
• Gauthier, Marie
• Kladde, Michael
• Brusko, Todd M
• Bihorac, Azra
• Moore, Frederick A
• Loftus, Tyler
• Bacher, Rhonda
• Moldawer, Lyle L
• Mohr, Alicia M
• Efron, Philip A

Titel

A Novel Single Cell RNA-seq Analysis of Non-Myeloid Circulating Cells in Late Sepsis

Ist Teil von

• Frontiers in immunology, 2021-08, Vol.12, p.696536-696536

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• With 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. A 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). We 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 fungal sepsis, such as greater expression of cytotoxic genes among CD8 T-lymphocytes in late bacterial sepsis. Circulating 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.