title: Differential Gamma Interferon- and Tumor Necrosis Factor Alpha-Driven Cytokine Response Distinguishes Acute Infection of a Metatherian Host with Toxoplasma gondii and Neospora caninum.
abstract: Toxoplasma gondiiandNeospora caninum(both Apicomplexa) are closely related cyst-forming coccidian parasites that differ significantly in their host ranges and ability to cause disease. Unlike eutherian mammals, Australian marsupials (metatherian mammals) have long been thought to be highly susceptible to toxoplasmosis and neosporosis because of their historical isolation from the parasites. In this study, the carnivorous fat-tailed dunnart (Sminthopsis crassicaudata) was used as a disease model to investigate the immune response and susceptibility to infection of an Australian marsupial toT. gondiiandN. caninumThe disease outcome was more severe inN. caninum-infected dunnarts than inT. gondii-infected dunnarts, as shown by the severity of clinical and histopathological features of disease and higher tissue parasite burdens in the tissues evaluated. Transcriptome sequencing (RNA-seq) of spleens from infected dunnarts and mitogen-stimulated dunnart splenocytes was used to define the cytokine repertoires. Changes in mRNA expression during the time course of infection were measured using quantitative reverse transcription-PCR (qRT-PCR) for key Th1 (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]), Th2 (interleukin 4 [IL-4] and IL-6), and Th17 (IL-17A) cytokines. The results show qualitative differences in cytokine responses by the fat-tailed dunnart to infection withN. caninumandT. gondiiDunnarts infected withT. gondiiwere capable of mounting a more effective Th1 immune response than those infected withN. caninum, indicating the role of the immune response in the outcome scenarios of parasite infection in this marsupial mammal.
authors.affiliation: Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, New South Wales, Australia.|School of Life and Environmental Sciences, Faculty of Science, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Donahoe
authors.affiliation: Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, New South Wales, Australia.|School of Life and Environmental Sciences, Faculty of Science, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: David N
authors.initials: DN
authors.lastname: Phalen
authors.affiliation: Discipline of Physiology and Bosch Institute, School of Medical Sciences, Faculty of Medicine, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Bronwyn M
authors.initials: BM
authors.lastname: McAllan
authors.affiliation: Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, New South Wales, Australia.|Centre for Animal Health Innovation, University of the Sunshine Coast, Sippy Downs, Queensland, Australia.
authors.forename: Denis
authors.initials: D
authors.lastname: O'Meally
authors.affiliation: School of Animal and Veterinary Sciences, University of Adelaide, Roseworthy, South Australia, Australia.
authors.forename: Milton M
authors.initials: MM
authors.lastname: McAllister
authors.affiliation: School of Life Sciences, University of Technology Sydney, Ultimo, New South Wales, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Ellis
authors.affiliation: Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, New South Wales, Australia jan.slapeta@sydney.edu.au.|School of Life and Environmental Sciences, Faculty of Science, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Jan
authors.identifier: http://orcid.org/0000-0003-1459-9117
authors.initials: J
authors.lastname: Šlapeta
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D003048:Coccidiosis / Q000276:immunology*; D004198:Disease Susceptibility; D007371:Interferon-gamma / Q000276:immunology*; D008394:Marsupialia / Q000276:immunology / Q000469:parasitology*; D018688:Neospora; D059208:Parasite Load; D060888:Real-Time Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000469:parasitology; D058408:Th1-Th2 Balance; D014122:Toxoplasma; D014124:Toxoplasmosis, Animal / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: apicomplexan parasites; cytokines; real-time PCR; transcriptomics