Unique lymphocyte transcriptomic profiles in septic patients with chronic critical illness

作者：Evan L. Barrios, Leandro Balzano‐Nogueira, Valerie E. Polcz, Christine Rodhouse, Jack R. Leary, Dijoia B. Darden, Jaimar C. Rincon, Marvin L. Dirain, Ricardo Ungaro, Dina C. Nacionales, Shawn D. Larson, Ashish K. Sharma, Gilbert R. Upchurch, Shannon M. Wallet, Todd M. Brusko, Tyler J. Loftus, Alicia M. Mohr, Robert Maile, Rhonda Bacher, Guoshuai Cai, Michael P. Kladde, Clayton E. Mathews, Lyle L. Moldawer, Maigan Brusko, Philip A. Efron · 发表于：Frontiers in Immunology · 年份：2024 · DOI：10.3389/fimmu.2024.1478471 · 被引用次数：6 · 研究领域：Sepsis Diagnosis and Treatment、Single-cell and spatial transcriptomics、Immune Response and Inflammation

Introduction Despite continued improvement in post-sepsis survival, long term morbidity and mortality remain high. Chronic critical illness (CCI), defined as persistent inflammation and organ injury requiring prolonged intensive care, is a harbinger of poor long-term outcomes in sepsis survivors. Current dogma states that sepsis survivors are immunosuppressed, particularly in CCI. Investigation of this immune suppression in heterogeneous immune populations across distinct clinical trajectories and outcomes, along with limited sampling access, is accessible via single-cell RNA sequencing (scRNA-seq). Methods scRNA-seq analysis was performed on healthy subjects (n=12), acutely septic patients at day 4 ± 1 (n=4), and those defined as rapid recovery (n=4) or CCI (n=5) at day 14-21. Differential gene expression and pathway analyses were performed on peripheral blood lymphocytes at both a population and annotated cell subset level. Cellular function was assessed via enzyme-linked immunosorbent spot (ELISpot), cytokine production analysis, and T-cell proliferation assays on an additional cohort of septic patients (19 healthy, 68 acutely septic, 27 rapid recovery and 20 classified as CCI 14-21 days after sepsis onset). Results Sepsis survivors that developed CCI exhibited proportional shifts within lymphoid cell populations, with expanded frequency of CD8 + and NK cells. Differential expression and pathway analyses revealed continued activation in T cells and NK cells, with generaliz...