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.
Highlights
Neospora caninum is a cyst-forming coccidian parasite responsible for clinical infections in a wide range of animal hosts including bovines[1]
We used wild-type (WT) C57BL/6 (B6) mice, which are susceptible to chronic neosporosis but resist acute infection[16], to determine whether CD8+ T cells are activated in the course of acute N. caninum infection, established by i.p. injection of 1 × 107 N. caninum tachyzoites (NcT)
This higher susceptibility was evident at a later time in 40-day infected mice. This result is in agreement with a previous study in which a mild effect in protecting mice against N. caninum infection was suggested for CD8+ T cells as assessed by using a CD8 T cell-depleting mAb9
Summary
Neospora caninum is a cyst-forming coccidian parasite responsible for clinical infections in a wide range of animal hosts including bovines[1]. Studies performed in mice and cattle infected with N. caninum have shown that dendritic cells and macrophages[4,5,6], NK cells[7,8] and CD4+ T cells[9,10,11] provide different effector functions in protective immunity to neosporosis. A study in which CD8+ T cells were depleted using a specific monoclonal antibody (mAb) revealed a mild protective effect of this lymphocyte population in N. caninum infected mice[9]. We confirmed that CD8+ T cells have a protective role in N. caninum infected hosts and provide compelling evidence showing that production of IFN-γ rather than cytotoxic function mediates their immunoprotective role
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