Induction of an IL7-R(+)c-Kit(hi) Myelolymphoid Progenitor Critically Dependent on IFN-gamma Signaling During Acute Malaria

Nat Immunol. 2010 Jun;11(6):477-85. doi: 10.1038/ni.1869. Epub 2010 May 2.

Abstract

Although the relationship between hematopoietic stem cells and progenitor populations has been investigated extensively under steady-state conditions, the dynamic response of the hematopoietic compartment during acute infection is largely unknown. Here we show that after infection of mice with Plasmodium chabaudi, a c-Kit(hi) progenitor subset positive for interleukin 7 receptor-alpha (IL-7Ralpha) emerged that had both lymphoid and myeloid potential in vitro. After being transferred into uninfected alymphoid or malaria-infected hosts, IL-7Ralpha(+)c-Kit(hi) progenitors generated mainly myeloid cells that contributed to the clearance of infected erythrocytes in infected hosts. The generation of these infection-induced progenitors was critically dependent on interferon-gamma (IFN-gamma) signaling in hematopoietic progenitors. Thus, IFN-gamma is a key modulator of hematopoiesis and innate and adaptive immunity during acute malaria infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Hematopoietic Stem Cells / immunology*
  • Humans
  • Immunity, Innate
  • Interferon-gamma / immunology*
  • Malaria / immunology*
  • Mice
  • Myeloid Progenitor Cells / immunology*
  • Plasmodium chabaudi
  • Proto-Oncogene Proteins c-kit / immunology*
  • Receptors, Interleukin-7 / immunology*
  • Signal Transduction*
  • T-Lymphocyte Subsets / immunology

Substances

  • Receptors, Interleukin-7
  • Interferon-gamma
  • Proto-Oncogene Proteins c-kit