Type I interferons drive inflammasome-independent emergency monocytopoiesis during endotoxemia

Sci Rep. 2017 Dec 5;7(1):16935. doi: 10.1038/s41598-017-16869-2.

Abstract

Emergency monocytopoiesis is an inflammation-driven hematological process that supplies the periphery with monocytes and subsequently with macrophages and monocyte-derived dendritic cells. Yet, the regulatory mechanisms by which early bone marrow myeloid progenitors commit to monocyte-derived phagocytes during endotoxemia remains elusive. Herein, we show that type I interferons signaling promotes the differentiation of monocyte-derived phagocytes at the level of their progenitors during a mouse model of endotoxemia. In this model, we characterized early changes in the numbers of conventional dendritic cells, monocyte-derived antigen-presenting cells and their respective precursors. While loss of caspase-1/11 failed to impair a shift toward monocytopoiesis, we observed sustained type-I-IFN-dependent monocyte progenitors differentiation in the bone marrow correlated to an accumulation of Mo-APCs in the spleen. Importantly, IFN-alpha and -beta were found to efficiently generate the development of monocyte-derived antigen-presenting cells while having no impact on the precursor activity of conventional dendritic cells. Consistently, the LPS-driven decrease of conventional dendritic cells and their direct precursor occurred independently of type-I-IFN signaling in vivo. Our characterization of early changes in mononuclear phagocytes and their dependency on type I IFN signaling during sepsis opens the way to the development of treatments for limiting the immunosuppressive state associated with sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Endotoxemia / chemically induced
  • Endotoxemia / metabolism
  • Endotoxemia / pathology*
  • Hematopoiesis
  • Inflammasomes / metabolism*
  • Interferon Type I / metabolism*
  • Lipopolysaccharides / toxicity
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / metabolism
  • Monocytes / pathology*
  • Receptor, Interferon alpha-beta / genetics
  • Receptors, IgG / metabolism
  • Spleen / pathology

Substances

  • Ifnar1 protein, mouse
  • Inflammasomes
  • Interferon Type I
  • Lipopolysaccharides
  • Receptors, IgG
  • Receptor, Interferon alpha-beta