title: Differential induction of TLR3-dependent innate immune signaling by closely related parasite species.
abstract: The closely related protozoan parasites Toxoplasma gondii and Neospora caninum display similar life cycles, subcellular ultrastructure, invasion mechanisms, metabolic pathways, and genome organization, but differ in their host range and disease pathogenesis. Type II (γ) interferon has long been known to be the major mediator of innate and adaptive immunity to Toxoplasma infection, but genome-wide expression profiling of infected host cells indicates that Neospora is a potent activator of the type I (α/β) interferon pathways typically associated with antiviral responses. Infection of macrophages from mice with targeted deletions in various innate sensing genes demonstrates that host responses to Neospora are dependent on the toll-like receptor Tlr3 and the adapter protein Trif. Consistent with this observation, RNA from Neospora elicits TLR3-dependent type I interferon responses when targeted to the host endo-lysosomal system. Although live Toxoplasma fail to induce type I interferon, heat-killed parasites do trigger this response, albeit much weaker than Neospora, and co-infection studies reveal that T. gondii actively suppresses the production of type I interferon. These findings reveal that eukaryotic pathogens can be potent inducers of type I interferon and that related parasite species interact with this pathway in distinct ways.
authors: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Daniel P
authors: DP
authors: Beiting
authors: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Lucia
authors: L
authors: Peixoto
authors: Department of Molecular Microbiology, Washington University, St. Louis, Missouri, United States of America.
authors: Natalia S
authors: NS
authors: Akopyants
authors: Department of Molecular Microbiology, Washington University, St. Louis, Missouri, United States of America.
authors: Stephen M
authors: SM
authors: Beverley
authors: Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: E John
authors: EJ
authors: Wherry
authors: Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: David A
authors: DA
authors: Christian
authors: Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Christopher A
authors: CA
authors: Hunter
authors: Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Igor E
authors: IE
authors: Brodsky
authors: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: David S
authors: DS
authors: Roos
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003048:Coccidiosis / Q000276:immunology* / Q000469:parasitology; D006790:Host-Parasite Interactions; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D018688:Neospora / Q000235:genetics / Q000502:physiology*; D051196:Toll-Like Receptor 3 / Q000276:immunology*; D014122:Toxoplasma / Q000235:genetics / Q000502:physiology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000469:parasitology
chemical_list: D007370:Interferon Type I; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3