title: NK cell-derived interferon-γ orchestrates cellular dynamics and the differentiation of monocytes into dendritic cells at the site of infection.
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.
authors: Laboratory of Experimental Immunology, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA. rgoldszmid@mail.nih.gov
authors: Romina S
authors: RS
authors: Goldszmid
authors: Pat
authors: P
authors: Caspar
authors: Aymeric
authors: A
authors: Rivollier
authors: Sandy
authors: S
authors: White
authors: Amiran
authors: A
authors: Dzutsev
authors: Sara
authors: S
authors: Hieny
authors: Brian
authors: B
authors: Kelsall
authors: Giorgio
authors: G
authors: Trinchieri
authors: Alan
authors: A
authors: Sher
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D002454:Cell Differentiation; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D017930:Genes, Reporter; D007371:Interferon-gamma / Q000502:physiology*; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000637:transplantation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000737:chemistry / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D009504:Neutrophils / Q000276:immunology; D010538:Peritonitis / Q000276:immunology / Q000469:parasitology; D010586:Phagocytes / Q000145:classification / Q000276:immunology / Q000473:pathology; D017471:Receptors, Interferon / Q000172:deficiency / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology; D000096743:Interferon gamma Receptor
chemical_list: D000950:Antigens, Ly; D007371:Interferon-gamma; D053762:Interleukin-12 Subunit p40; D053594:Myeloid Differentiation Factor 88; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D000096743:Interferon gamma Receptor; C494192:Ly-6C antigen, mouse; C507780:Myd88 protein, mouse