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Although its effects on specific cell types have been well studied in vitro, its in vivo effects are less clearly understood because of its diverse actions on many different cell types. Although control of multiple protozoan parasites is thought to depend critically on the direct action of IFN-\u03b3 on macrophages, this premise has never been directly proven in vivo. To more directly examine the effects of IFN-\u03b3 on cells of the macrophage lineage in vivo, we generated mice called the \u201cmacrophages insensitive to IFN-\u03b3\u201d (MIIG) mice, which express a dominant negative mutant IFN-\u03b3 receptor in CD68+ cells: monocytes, macrophages, dendritic cells, and mast cells. Macrophage lineage cells and mast cells from these mice are unable to respond to IFN-\u03b3, whereas other cells are able to produce and respond to this cytokine normally. When challenged in vitro, macrophages from MIIG mice were unable produce NO or kill Trypanosoma cruzi or Leishmania major after priming with IFN-\u03b3. Furthermore, MIIG mice demonstrated impaired parasite control and heightened mortality after T. cruzi, L. major, and Toxoplasma gondii infection, despite an appropriate IFN-\u03b3 response. In contrast, MIIG mice displayed normal control of lymphocytic choriomeningitis virus, despite persistent insensitivity of macrophages to IFN-\u03b3. Thus, the MIIG mouse formally demonstrates for the first time in vivo, the specific importance of direct, IFN-\u03b3 mediated activation of macrophages for controlling infection with multiple protozoan parasites.<\/jats:p>","DOI":"10.4049\/jimmunol.0902346","type":"journal-article","created":{"date-parts":[[2009,12,14]],"date-time":"2009-12-14T22:19:26Z","timestamp":1260829166000},"page":"877-885","source":"Crossref","is-referenced-by-count":87,"title":["Mice with a Selective Impairment of IFN-\u03b3 Signaling in Macrophage Lineage Cells Demonstrate the Critical Role of IFN-\u03b3\u2013Activated Macrophages for the Control of Protozoan Parasitic Infections In Vivo"],"prefix":"10.1093","volume":"184","author":[{"given":"Jennifer E","family":"Lykens","sequence":"first","affiliation":[{"name":"Division of Immunobiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine E","family":"Terrell","sequence":"additional","affiliation":[{"name":"Division of Immunobiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E","family":"Zoller","sequence":"additional","affiliation":[{"name":"Division of Immunobiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senad","family":"Divanovic","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelien","family":"Trompette","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L","family":"Karp","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Aliberti","sequence":"additional","affiliation":[{"name":"Division of Molecular Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J","family":"Flick","sequence":"additional","affiliation":[{"name":"Division of Rheumatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B","family":"Jordan","sequence":"additional","affiliation":[{"name":"Division of Immunobiology"},{"name":"Division of Bone Marrow Transplant and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,27]]},"reference":[{"key":"2026012808102232700_r1","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1146\/annurev.immunol.15.1.563","article-title":"The IFN \u03b3 receptor: a paradigm for cytokine receptor signaling.","volume":"15","author":"Bach","year":"1997","journal-title":"Annu. 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