title: Diverse roles for T-bet in the effector responses required for resistance to infection.
abstract: The transcription factor T-bet has been most prominently linked to NK and T cell production of IFN-γ, a cytokine required for the control of a diverse array of intracellular pathogens. Indeed, in mice challenged with the parasite Toxoplasma gondii, NK and T cell responses are characterized by marked increases of T-bet expression. Unexpectedly, T-bet(-/-) mice infected with T. gondii develop a strong NK cell IFN-γ response that controls parasite replication at the challenge site, but display high parasite burdens at secondary sites colonized by T. gondii and succumb to infection. The loss of T-bet had a modest effect on T cell production of IFN-γ but did not impact on the generation of parasite-specific T cells. However, the absence of T-bet resulted in lower T cell expression of CD11a, Ly6C, KLRG-1, and CXCR3 and fewer parasite-specific T cells at secondary sites of infection, associated with a defect in parasite control at these sites. Together, these data highlight T-bet-independent pathways to IFN-γ production and reveal a novel role for this transcription factor in coordinating the T cell responses necessary to control this infection in peripheral tissues.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Gretchen
authors.initials: G
authors.lastname: Harms Pritchard
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Aisling O'Hara
authors.initials: AO
authors.lastname: Hall
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: David A
authors.initials: DA
authors.lastname: Christian
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Sagie
authors.initials: S
authors.lastname: Wagage
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Qun
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Gaia
authors.initials: G
authors.lastname: Muallem
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Beena
authors.initials: B
authors.lastname: John
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Arielle
authors.initials: A
authors.lastname: Glatman Zaretsky
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: William G
authors.initials: WG
authors.lastname: Dunn
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104;
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Perrigoue
authors.affiliation: Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, NY 10032; and Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, NY 10032.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Reiner
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104; chunter@vet.upenn.edu.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hunter
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000235:genetics* / Q000276:immunology*; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D007109:Immunity; D007111:Immunity, Cellular; D007113:Immunity, Innate; D016130:Immunophenotyping; D007239:Infections / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor