Editors' ChoiceSepsis

Hematopoietic maladaptation facilitates septic screening

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Science Translational Medicine  11 Mar 2020:
Vol. 12, Issue 534, eabb2768
DOI: 10.1126/scitranslmed.abb2768

Abstract

Single-cell RNA sequencing of peripheral blood cells from patients with bacterial infections reveals a monocyte subset that can distinguish those at risk of sepsis.

The human immune system is a complex and evolving ecosystem that uniquely responds to challenges, such as infection, through coordinated responses. Dysregulation of these responses can lead to sepsis, for which no diagnostic biomarkers or effective therapies currently exist. The cell types and molecular controllers that confer this condition have remained elusive, owing to heterogeneity of the infectious pathogens and personalized immune responses.

To further elucidate positive and negative effectors and cell state transitions that distinguish the immune response in sepsis from bacterial infections [including urinary-tract infection (UTI)], Reyes and co-workers utilized single-cell RNA sequencing on peripheral blood of patients with UTI with and without signs of sepsis. The authors observed sixteen cell states encompassing T cells, B cells, natural killer cells, dendritic cells, and monocytes and found certain cell types associated with disease state. In particular, the authors identified expansion of a CD14+ metabolically distinct monocyte state in septic patients and further contrasted gene signatures of this subset of cells with published studies of sepsis across different locations, genetic backgrounds, and clinical contexts. The authors then used a set of surface markers (CD14+/HLA-DRlow/IL1R2high) to enrich the cells; they showed that the subset is derived from bone marrow precursors that differentiate with an aberrant epigenomic landscape.

The ability to distinguish a cell subtype and specific genes in patients who are at risk for sepsis can potentially enable patient stratification and therapeutic targeting. Additional studies are needed to determine if this subset of monocytes directly contribute to organ dysfunction in sepsis and if specific metabolites found in the bloodstream drive development of this cell subtype’s epigenomic landscape. However, given the high mortality associated with sepsis, these promising results should find translation as a screening tool and during routine monitoring.

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