Microarray analyses of mouse responses to infection by Neospora caninum identifies disease associated cellular pathways in the host response

Neospora caninum is a coccidian cyst-forming parasite found in a wide range of host species such as mice, dogs and cattle. The development of methods such as vaccines to prevent abortion and fetal loss due to neosporosis would be greatly assisted by further knowledge on immunity and host responses to infection. In this study we used microarray technology to investigate the protective host responses occurring at 6h post infection in the spleen of mice infected with a prototype live N. caninum vaccine. Naive non-pregnant mice were infected with the NC-Nowra isolate as such infections are known to induce protective host responses that will prevent transplacental transmission of a challenge given using pregnancy. The expression data was analysed by SAM (significance of microarrays), ANOVA and clustering methods. Gene lists were investigated for enrichment of gene ontology terms by functional annotation using hypergeometric tests. The results show that Qs and BALB/c mice infected with NC-Nowra differ in their transcriptional responses to infection and these affect a wide range of biological and molecular processes. Transcriptional changes in the Jak-STAT signaling pathway (as well as Irf and other IFN-γ regulated molecules such as GTPases) confirmed the influence of IFN-γ in the mouse response to N. caninum. Gene ontology analyses also assigned some of the molecules involved to well known disease pathways associated with cancer, Parkinson's and Alzheimer's diseases, which were linked to the cell cycle, mitochondrial electron transport chain and coupled proton transport pathways amongst others. Although infection of mice with NC-Nowra causes little or no signs of clinical disease, the molecular functions, processes and pathways identified through these studies clearly warrant further investigation for their role in the development of protective immunity as well as pathogenesis. These studies therefore provide new, exciting leads by which to study neosporosis.