title: Predominant role of interferon-γ in the host protective effect of CD8(+) T cells against Neospora caninum infection.
abstract: It is well established that CD8(+) T cells play an important role in protective immunity against protozoan infections. However, their role in the course of Neospora caninum infection has not been fully elucidated. Here we report that CD8-deficient mice infected with N. caninum presented higher parasitic loads in the brain and lungs and lower spleen and brain immunity-related GTPases than their wild-type counterparts. Moreover, adoptive transfer of splenic CD8(+) T cells sorted from N. caninum-primed immunosufficient C57BL/10 ScSn mice prolonged the survival of infected IL-12-unresponsive C57BL/10 ScCr recipients. In both C57BL/6 and C57BL/10 ScSn mice CD8(+) T cells are activated and produce interferon-γ (IFN-γ) upon challenged with N. caninum. The host protective role of IFN-γ produced by CD8(+) T cells was confirmed in N. caninum-infected RAG2-deficient mice reconstituted with CD8(+) T cells obtained from either IFN-γ-deficient or wild-type donors. Mice receiving IFN-γ-expressing CD8(+) T cells presented lower parasitic burdens than counterparts having IFN-γ-deficient CD8(+) T cells. Moreover, we observed that N. caninum-infected perforin-deficient mice presented parasitic burdens similar to those of infected wild-type controls. Altogether these results demonstrate that production of IFN-γ is a predominant protective mechanism conferred by CD8(+) T cells in the course of neosporosis.
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, and IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Correia
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, and IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal.|ICBAS - Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Ferreirinha
authors.affiliation: ICBAS - Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.
authors.forename: Sofia
authors.initials: S
authors.lastname: Botelho
authors.affiliation: ICBAS - Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Belinha
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, and IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Leitão
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
authors.forename: Íris
authors.initials: Í
authors.lastname: Caramalho
authors.affiliation: ICBAS - Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.|UMIB-Unidade Multidisciplinar de Investigação Biomédica, Universidade do Porto, Porto.
authors.forename: Luzia
authors.initials: L
authors.lastname: Teixeira
authors.affiliation: Inmunología, Centro de Investigaciones Biomédicas (CINBIO), Instituto de Investigación Biomédica, Universidade de Vigo, Campus Lagoas Marcosende, E-36200 Vigo, Spain.
authors.forename: África
authors.initials: Á
authors.lastname: González-Fernandéz
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, and IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal.|ICBAS - Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Appelberg
authors.affiliation: Instituto de Investigação e Inovação em Saúde, Universidade do Porto, and IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, 4150-180 Porto, Portugal.|ICBAS - Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Vilanova
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D002522:Chlorocebus aethiops; D003048:Coccidiosis / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006790:Host-Parasite Interactions / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018688:Neospora / Q000276:immunology* / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D014709:Vero Cells
chemical_list: D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse