The Post-Septic Peripheral Myeloid Compartment Reveals Unexpected Diversity in Myeloid-Derived Suppressor Cells

Abstract Sepsis 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. The 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. Using Cellular Indexing of Transcriptomes and Epitopes by Sequencing followed by transcriptomic analysis, we 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. Competing Interest Statement The authors have declared no competing interest. Funding Statement This work was supported, in part, by the following National Institutes of Health grants: National Institutes of Health grant RM1 GM139690 (LLM, PAE, MK, CM) National Institutes of Health grant R35 GM140806 (PAE) National Institute of General Medical Sciences grant R35 GM146895 (RB) National Institute of General Medical Sciences postgraduate training grant T32 GM-008721 (EB, DBD, VP, JM) National Institute of General Medical Sciences postgraduate training grant T32 HL160491 (GG) Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of the University of Florida gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes 12 Data availability The datasets generated for this study can be found in the Gene Expression Omnibus (in-process). All analysis codes are available upon request.