Toxoplasma gondii is a prevalent obligate intracellular parasite which chronically infects more than a third of the world’s population. Key to parasite prevalence is its ability to form chronic and nonimmunogenic bradyzoite cysts, which typically form in the brain and muscle cells of infected mammals, including humans. While acute clinical infection typically involves neurological and/or ocular damage, chronic infection has been more recently linked to behavioral changes. Establishment and maintenance of chronic infection involves a balance between the host immunity and parasite evasion of the immune response. Here, we outline the known cellular interplay between Toxoplasma gondii and cells of the central nervous system and review the reported effects of Toxoplasma gondii on behavior and neurological disease. Finally, we review new technologies which will allow us to more fully understand host-pathogen interactions. 1. Introduction Toxoplasma gondii belongs to the phylum Apicomplexa, which consists of intracellular parasites having a characteristically polarized cell structure and a complex cytoskeletal and organellar arrangement at their apical end [1]. This obligate intracellular parasite can infect and replicate within virtually any nucleated mammalian or avian cell [2, 3]. It is believed that the major transmission method of T. gondii to humans is the consumption of raw or rare meat [4–6]. In addition, vertical transmission of T. gondii is also possible, occurring when a female receives a primary infection while pregnant which can lead to fetal morbidity such as hydrocephaly. Indeed, T. gondii infection is a primary cause of fetal malformations in the United States [7]. Up to 80% of a population may be infected, depending on eating habits and exposure to felines, which serve as the definitive hosts and shed environmentally robust oocysts in feces [7, 8]. Oocysts can be stable in the environment for up to a year, may contaminate food or water supplies, and infect other warm blooded vertebrates [9]. A recent study suggested that oocyst-acquired infections are the most clinically severe form of infection, which may occur not just through direct cat fecal exposure, but contamination of municipal drinking water [10]. Two critical intracellular stages in the pathogenesis and transmission of Toxoplasma gondii are the rapidly replicating tachyzoite stage and the slower growing, cyst-forming bradyzoite stage. Initially, latent infections in humans were assumed to be largely asymptomatic. However, during the initial AIDS crisis, Toxoplasma became known as a
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