NK cell-derived interferon-γ orchestrates cellular dynamics and the differentiation of monocytes into dendritic cells at the site of infection

Immunity. 2012 Jun 29;36(6):1047-59. doi: 10.1016/j.immuni.2012.03.026.

Abstract

Dendritic cells (DCs), monocytes, and/or macrophages initiate host-protective immune responses to intracellular pathogens in part through interleukin-12 (IL-12) production, although the relative contribution of tissue resident versus recruited cells has been unclear. Here, we showed that after intraperitoneal infection with Toxoplasma gondii cysts, resident mononuclear phagocytes are replaced by circulating monocytes that differentiate in situ into inflammatory DCs (moDCs) and F4/80(+) macrophages. Importantly, NK cell-derived interferon-γ (IFN-γ) was required for both the loss of resident mononuclear phagocytes and the local differentiation of monocytes into macrophages and moDCs. This newly generated moDC population and not the resident DCs (or macrophages) served as the major source of IL-12 at the site of infection. Thus, NK cell-derived IFN-γ is important in both regulating inflammatory cell dynamics and in driving the local differentiation of monocytes into the cells required for initiating the immune response to an important intracellular pathogen.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Ly / analysis
  • Cell Differentiation
  • Chemotaxis, Leukocyte
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Dendritic Cells / transplantation
  • Genes, Reporter
  • Interferon-gamma / physiology*
  • Interleukin-12 Subunit p40 / biosynthesis
  • Interleukin-12 Subunit p40 / genetics
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / transplantation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Monocytes / chemistry
  • Monocytes / immunology*
  • Monocytes / pathology
  • Monocytes / transplantation
  • Myeloid Differentiation Factor 88 / physiology
  • Neutrophils / immunology
  • Peritonitis / immunology
  • Peritonitis / parasitology
  • Phagocytes / classification
  • Phagocytes / immunology
  • Phagocytes / pathology
  • Receptors, Interferon / deficiency
  • Receptors, Interferon / physiology
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Specific Pathogen-Free Organisms
  • T-Lymphocyte Subsets / immunology
  • Toxoplasmosis, Animal / immunology

Substances

  • Antigens, Ly
  • Interleukin-12 Subunit p40
  • Ly-6C antigen, mouse
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Interferon
  • Recombinant Fusion Proteins
  • interferon gamma receptor
  • Interferon-gamma