Open Access
Vet. Res.
Volume 40, Number 4, July-August 2009
Number of page(s) 12
Published online 03 April 2009
How to cite this article Vet. Res. (2009) 40:32
How to cite this article: Vet. Res. (2009) 40:32
DOI: 10.1051/vetres/2009015

Myeloid differentiation factor 88 is required for resistance to Neospora caninum infection

Tiago W.P. Mineo1, 2, Luciana Benevides1, Neide M. Silva2 and João S. Silva1

1  Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900 - Ribeirão Preto, SP, Brazil
2  Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, MG, Brazil

Received 5 August 2008; accepted 27 March 2009; published online 03 April 2009

Abstract - Neospora caninum is an intracellular parasite that causes major economic impact on cattle raising farms, and infects a wide range of warm-blooded hosts worldwide. Innate immune mechanisms that lead to protection against this parasite are still unknown. In order to investigate whether myeloid differentiation factor 88 (MyD88) is required for resistance against N. caninum, genetically deficient mice (MyD88-/-) and wild type littermates were infected with live tachyzoites and the resistance to infection was evaluated. We found that sub-lethal tachyzoite doses induced acute mortality of MyD88-/- mice, which succumbed to infection due to uncontrolled parasite replication. Higher parasitism in MyD88-/- mice was associated with the lack of IL-12 production by dendritic cells, delayed IFN-$\gamma$ responses by NKT, CD4+ and CD8+ T lymphocytes, and production of high levels of IL-10. MyD88-/- mice replenished with IL-12 and IFN-$\gamma$ abolished susceptibility as the animals survived throughout the experimental period. We conclude that protective IFN-$\gamma$-mediated immunity to N. caninum is dependent on initial MyD88 signaling, in a mechanism triggered by production of IL-12 by dendritic cells. Further knowledge on Toll-like receptor recognition of N. caninum antigens is encouraged, since it could generate new prophylactic and therapeutic tools to control parasite burden.

Key words: Neospora caninum / innate immunity / MyD88 / IL-12 / IFN-$\gamma$

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© INRA, EDP Sciences 2009