Abstract

Toxoplasma gondii chronic infection in rodent secondary hosts has been reported to lead to a loss of innate, hard-wired fear toward cats, its primary host. However the generality of this response across T. gondii strains and the underlying mechanism for this pathogen-mediated behavioral change remain unknown. To begin exploring these questions, we evaluated the effects of infection with two previously uninvestigated isolates from the three major North American clonal lineages of T. gondii, Type III and an attenuated strain of Type I. Using an hour-long open field activity assay optimized for this purpose, we measured mouse aversion toward predator and non-predator urines. We show that loss of innate aversion of cat urine is a general trait caused by infection with any of the three major clonal lineages of parasite. Surprisingly, we found that infection with the attenuated Type I parasite results in sustained loss of aversion at times post infection when neither parasite nor ongoing brain inflammation were detectable. This suggests that T. gondii-mediated interruption of mouse innate aversion toward cat urine may occur during early acute infection in a permanent manner, not requiring persistence of parasite cysts or continuing brain inflammation.

Highlights

  • Toxoplasma gondii is a highly prevalent and successful neurotropic protozoan parasite that infects mammals and birds and is found nearly everywhere in the world [1,2]

  • Behavioral studies comparing infected and uninfected mice have suggested that rodents lose their innate, hard-wired fear of cat odors when chronically infected with T. gondii [5,6,7], presumably enhancing the transmission of the parasite to its primary host

  • Most T. gondii strains found in North America and Europe can be categorized into three well-defined clonal lineages called Type I, Type II, and Type III [8,9,10]

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Summary

Introduction

Toxoplasma gondii is a highly prevalent and successful neurotropic protozoan parasite that infects mammals and birds and is found nearly everywhere in the world [1,2]. The majority of behavioral studies have used Type II strains, which are known to result in high parasite-cyst loads in the brains of mice and cause correspondingly high levels of immune-mediated brain inflammation [11,12,13]. In preliminary experiments with male and female Balb/c mice, chronic infection with two Type II parasite strains (Pru and ME49) caused loss of innate aversion to bobcat urine (unpublished data).

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