Frontiers in Immunology (Apr 2024)
The post-septic peripheral myeloid compartment reveals unexpected diversity in myeloid-derived suppressor cells
- 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. Gauthier,
- 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
Affiliations
- Evan L. Barrios
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Jack R. Leary
- Department of Biostatistics, University of Florida College of Medicine and Public Health and Health Sciences, Gainesville, FL, United States
- Dijoia B. Darden
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Jaimar C. Rincon
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Micah Willis
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Valerie E. Polcz
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Gwendolyn S. Gillies
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Jennifer A. Munley
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Marvin L. Dirain
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Ricardo Ungaro
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Dina C. Nacionales
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Marie-Pierre L. Gauthier
- Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL, United States
- Shawn D. Larson
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Laurence Morel
- Department of Microbiology and Immunology, University of Texas San Antonio School of Medicine, San Antonio, TX, United States
- Tyler J. Loftus
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Alicia M. Mohr
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Robert Maile
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Michael P. Kladde
- Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL, United States
- Clayton E. Mathews
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, United States
- Maigan A. Brusko
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, United States
- Todd M. Brusko
- Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, United States
- Lyle L. Moldawer
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- Rhonda Bacher
- Department of Biostatistics, University of Florida College of Medicine and Public Health and Health Sciences, Gainesville, FL, United States
- Philip A. Efron
- Sepsis and Critical Illness Research Center, Department of Surgery, University of Florida College of Medicine, Gainesville, FL, United States
- DOI
- https://doi.org/10.3389/fimmu.2024.1355405
- Journal volume & issue
-
Vol. 15
Abstract
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.
Keywords
- myeloid-derived suppressor cells
- sepsis
- transcriptomics
- single-cell RNA sequencing
- chronic critical illness
