Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis

Sepsis arises from diverse and incompletely understood dysregulated host response processes following infection that leads to life-threatening organ dysfunction. Here we showed that neutrophils and emergency granulopoiesis drove a maladaptive response during sepsis. We generated a whole-blood single-cell multiomic atlas (272,993 cells, n = 39 individuals) of the sepsis immune response that identified populations of immunosuppressive mature and immature neutrophils. In co-culture, CD66b+ sepsis neutrophils inhibited proliferation and activation of CD4+ T cells. Single-cell multiomic mapping of circulating hematopoietic stem and progenitor cells (HSPCs) (29,366 cells, n = 27) indicated altered granulopoiesis in…

• W
  Wellcome

  Award: 204969/Z/16/Z
• WT
  Wellcome Trust

  Awards: 203141/Z/16/Z, Z/17/Z, 209422/Z/17/Z, 204969/Z/16/Z, 090532, 203141, 090532/Z/09/Z, 090532/Z/09/
• NI
  National Institute for Health and Care Research

  Award: 203141/Z/16/Z
• UO
  University of Oxford
• CF
  Croucher Foundation
• CA
  Chinese Academy of Medical Sciences

  Award: 2018-I2M-2-002
• MR
  Medical Research Council

  Awards: MR/V002503/1, 203141/Z/16/Z, MR/V002503/1, MR/X000605/1