Abstract
Subacute and chronic infections with the intracellular protozoan parasite Toxoplasma gondii are associated with an increased risk of psychiatric diseases like schizophrenia. However, little is known about the mechanisms involved in T. gondii-induced neuronal disorders. Recently, we reported that Toll-like receptor 2 (TLR2) was required to initiate the innate immune response in cultured mouse brain cells. However, how TLR2 contributes to latent infection with T. gondii remains unclear. Therefore, we examined the role of TLR2 in brain pathology and behavior using wild-type (TLR2+/+) and TLR2-deficient (TLR2-/-) mice. The behavioral analyses showed that TLR2 deficiency increased the anxiety state of the uninfected and infected animals alike, and TLR2 deficiency showed no relationship with the infection. In the contextual and cued fear-conditioning tests, T. gondii infection decreased the mouse freezing reaction while TLR2 deficiency increased it, but there was no interaction between the two factors. Our histopathological analysis showed that the TLR2+/+ and TLR2-/- mice had similar brain lesions at 30 days post infection (dpi) with T. gondii. Higher numbers of parasites were detected in the brains of the TLR2-/- mice than in those from the TLR2+/+ mice at 30 dpi, but not at 7 and 14 dpi. No significant differences were observed in the proinflammatory gene expression levels in the TLR2+/+ and TLR2-/- mice. Therefore, it appears that TLR2 signaling in the brain might contribute to the control of parasite growth, but not to brain pathology or the impaired fear memory response induced by infection with T. gondii.
Highlights
Until now, most studies on the roles played by Toll-like receptors (TLRs) have been focused on the immune system, but it is known that TLRs play important roles in neurodevelopment, adult neurogenesis, neuroplasticity, as well as in learning and memory [1]
We recently showed that Toll-like receptor 2 (TLR2) regulates many genes in primary cultured astrocytes, microglia, and neurons during Toxoplasma gondii infection, especially the innate immune response genes, suggesting that TLR2 plays an important role in host resistance to CNS infections with T. gondii [9]
To the best of our knowledge, this is the first study to investigate the effects of TLR2 deficiency on latent Toxoplasma infections in mice
Summary
Most studies on the roles played by Toll-like receptors (TLRs) have been focused on the immune system, but it is known that TLRs play important roles in neurodevelopment, adult neurogenesis, neuroplasticity, as well as in learning and memory [1]. Toll-like receptor 2 and Toxoplasma infection (24880006) (to S.T.), a Grant-in- Aid for Young Scientists (18K14577) (to F.I.), and a research fellowship (15J03171) (to F.I.) from the Japan Society for the Promotion of Science, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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