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.
|Advisor:||Robey, Ellen A., Eisen, Michael B.|
|Commitee:||Bautista, Diana M., Kaufer, Daniela|
|School:||University of California, Berkeley|
|Department:||Molecular & Cell Biology|
|School Location:||United States -- California|
|Source:||DAI-B 78/11(E), Dissertation Abstracts International|
|Subjects:||Molecular biology, Behavioral psychology, Immunology|
|Keywords:||Behavioral neuroimmunology, Mouse innate behavior, Parasite manipulation, Toxoplasma gondii|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be