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

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 those patients who develop chronic critical illness. The origins and lineage of these MDSC subpopulations were previously assumed to be linear, discrete, and unidirectional; however, these cells exhibit a dynamic phenotype with considerable plasticity. Using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) 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. A mixture of whole blood myeloid-enriched and Ficoll-enriched peripheral blood mononuclear cells from 4 early septic patients (day 4), 10 late septic patients (post-sepsis day 14-21, RAP n=5 and CCI n=5) and 12 healthy subjects underwent Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq). ADT; Oligo Sequence Biolegend_307663_C0159 HLADR; AATAGCGAGCAAGTA Biolegend_300479_C0034 CD3; CTCATTGTAACTCCT Biolegend_323053_C0392 CD15; TCACCAGTACCTAGT Biolegend_351356_C0390 CD127; GTGTGTTGTCCTATG Biolegend_353747_C0140 CD183; GCGATGGTAGATTAT Biolegend_392909_C0166 CD66B; AGCTGTAAGTTTCGG Biolegend_300567_C0072 CD4; TGTTCCCGCTCAACT Biolegend_301859_C0081 CD14; TCTCAGACCTCCGTA Biolegend_353440_C0143 CD196; GATCCCTTTGTCACT Biolegend_302649_C0085 CD25; TTTGTCCTGTACGCC Biolegend_301359_C0161 CD11B; GACAAGTGATCTGCA