Abstract
BackgroundToxoplasma gondii is an intracellular parasite that can modulate host responses and presumably host behavior. Host responses as well as pathogenesis vary depending on the parasite strains that are responsible for infection. In immune competent individuals, T. gondii preferentially infects tissues of the central nervous systems (CNS), which might be an additional factor in certain psychiatric disorders. While in immune-compromised individuals and pregnant women, the parasite can cause life-threatening infections. With the availability of the genome-wide investigation platform, the global responses in gene expression of the host after T. gondii infection can be systematically investigated.MethodsTotal RNA of brain tissues and peripheral lymphocytes of BALB/C mice infected with RH and ME 49 strain T. gondii as well as that of healthy mice were purified and converted to cRNA with incorporated Cy5-CTP (experimental samples), or Cy3-CTP (control samples). The labeled cRNA probes were hybridized to the Whole Mouse Genome Microarray. The impact of parasite infection on gene expression in both brain tissues and peripheral lymphocytes were analyzed. Differentially expressed genes were revalidated with real-time quantitative reverse transcriptase-polymerase chain reaction (Q-PCR).ResultsData indicated that the genes associated with immunity were up-regulated after infection by the two parasite strains, but significant up-regulation was observed in both brain tissues and peripheral lymphocytes of mice infected with ME49 strain compared to that infected by RH strain. The pathways related to pathogenesis of the nervous system were more significantly up-regulated in mice infected with RH strain.ConclusionsGenetically distinct T. gondii strains showed clear differences in modulation of host pathophysiological and immunological responses in both brain tissue and peripheral lymphocytes. It was likely that some of the host responses to T. gondii infection were universal, but the immune response and CNS reaction were in a strain-specific manner.
Highlights
Toxoplasma gondii is an intracellular parasite that can modulate host responses and presumably host behavior
Significant transcriptomic changes in mice infected by RH and ME49 strain T. gondii Discriminant analysis demonstrated significant changes in the transcriptome of brain tissue and peripheral lymphocytes of mice before and after T. gondii infection of RH and ME49 strain (Table 2)
Of the 41,174 genes presented in the mouse genome microarray, we identified 1,537 up-regulated and 1,213 down-regulated genes in brain tissues (Additional file 1), and 3,602 upregulated and 4,045 down-regulated genes in peripheral lymphocytes in the group of mice as a result of infection by T. gondii RH strain, compared to healthy control samples (Additional file 2) (p ≤ 0.05)
Summary
Toxoplasma gondii is an intracellular parasite that can modulate host responses and presumably host behavior. With the availability of the genome-wide investigation platform, the global responses in gene expression of the host after T. gondii infection can be systematically investigated. Toxoplasma gondii is an obligatory intracellular parasite that causes diverse pathological effects in humans and other warm-blooded vertebrates [1,2]. Type I strain, such as RH strain is considered as the most virulent in mice, and it has been frequently found in individuals at risk of atypical ocular toxoplasmosis [4]. Type III T. gondii is rarely found in humans, but the reason is unclear [6]. 80% of individuals are asymptomatic after T. gondii infection, partially due to effective innate responses [7]. Studies have found that parasites of type I strains grow faster in vitro than that of type II or III strains [9]
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