Journal article
NK cell-derived interferon-γ orchestrates the cellular dynamics and differentiation of monocytes into inflammatory dendritic cells at the site of infection
Laboratory of Experimental Immunology, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 217021
Immunobiology Section, Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, MD 208922
Mucosal Immunobiology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 208923
Dendritic cells (DCs), monocyte 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.
| Language: | Undetermined |
|---|---|
| Year: | 2013 |
| Pages: | 1047-1059 |
| ISSN: | 10974180 and 10747613 |
| Types: | Journal article |
| DOI: | 10.1016/j.immuni.2012.03.026 |
Adoptive Transfer Animals Antigens, Ly Cell Differentiation Chemotaxis, Leukocyte Dendritic Cells Genes, Reporter Interferon gamma Receptor Interferon-gamma Interleukin-12 Subunit p40 Killer Cells, Natural Ly-6C antigen, mouse Macrophages, Peritoneal Mice Mice, Inbred BALB C Mice, Inbred C57BL Monocytes Myd88 protein, mouse Myeloid Differentiation Factor 88 Neutrophils Peritonitis Phagocytes Receptors, Interferon Recombinant Fusion Proteins Specific Pathogen-Free Organisms T-Lymphocyte Subsets Toxoplasmosis, Animal
