UC Berkeley

Toxoplasma gondii infection-induced Loss of Innate Aversion to Cat Urine in Mice

by

Wendy Marie Ingram

Doctor of Philosophy in Molecular & Cell Biology

University of California, Berkeley

Professor Ellen Robey, Co-chair

Professor Michael Eisen, Co-chair

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 remains 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. We investigated the role of the mouse immune system in this behavior manipulation and identify that interleukin 4 (IL4) is a key molecule required for the loss of innate aversion to cat urine. Characterization of the source of IL4 in mice following infection has revealed that there are a number of cell types from which the critical IL4 could be produced. Initial T cell transfer experiments suggest that CD4 T cells capable of making IL4 may be partially involved in mediating the behavior manipulation.