The post-septic peripheral myeloid compartment reveals unexpected diversity in myeloid-derived suppressor cells

• DOI: 10.3389/fimmu.2024.1355405
• Publication Date: 2024-04-24T04:37:23Z
• Authors: Evan L. Barrios; Jack R. Leary; Dijoia B. Darden; Jaimar C. Rincon; Micah Willis; Valerie E. Polcz; Gwendolyn S. Gillies; Jennifer A. Munley; Marvin L. Dirain; Ricardo Ungaro; Dina C. Nacionales; Marie-Pierre L. G...; Shawn D. Larson; Laurence Morel; Tyler J. Loftus; Alicia M. Mohr; Robert Maile; Michael P. Kladde; Clayton E. Mathews; Maigan A. Brusko; Todd M. Brusko; Lyle L. Moldawer; Rhonda Bacher; Philip A. Efron
• Keywords: Male; 0303 health sciences; Myeloid-Derived Suppressor Cells; Gene Expression Profiling; Immunology; Cell Differentiation; RC581-607; myeloid-derived suppressor cells; single-cell RNA sequencing; sepsis; transcriptomics; 03 medical and health sciences; chronic critical illness; Sepsis; Humans; Female; Immunologic diseases. Allergy; Transcriptome

IntroductionSepsis engenders distinct host immunologic changes that include the expansion of myeloid-derived suppressor cells (MDSCs). These cells play a physiologic role in tempering acute inflammatory responses but can persist in patients who develop chronic critical illness.MethodsCellular Indexing of Transcriptomes and Epitopes by Sequencing and transcriptomic analysis are used to describe MDSC subpopulations based on differential gene expression, RNA velocities, and biologic process clustering.ResultsWe identify a unique lineage and differentiation pathway for MDSCs after sepsis and describe a novel MDSC subpopulation. Additionally, we report that the heterogeneous response of the myeloid compartment of blood to sepsis is dependent on clinical outcome.DiscussionThe origins and lineage of these MDSC subpopulations were previously assumed to be discrete and unidirectional; however, these cells exhibit a dynamic phenotype with considerable plasticity.