Mice Infected with Low-virulence Strains of Toxoplasma gondii Lose their Innate Aversion to Cat Urine, Even after Extensive Parasite Clearance

TL;DR

This study demonstrates that infection with various strains of Toxoplasma gondii causes mice to lose their innate fear of cat urine, with effects persisting even after the parasite is cleared, indicating a permanent behavioral change.

Contribution

It reveals that loss of aversion is a common trait across major T. gondii strains and occurs independently of ongoing infection or inflammation.

Findings

Loss of aversion is caused by infection with any of the three major T. gondii lineages.

Attenuated Type I infection results in lasting loss of aversion even after parasite clearance.

Behavioral change occurs during early infection and persists permanently.

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 parasitecysts or continuing brain inflammation.