Neuroinflammation-Associated Aspecific Manipulation of Mouse Predator Fear by Toxoplasma gondii

Abstract

Summary: In rodents, the decrease of felid aversion induced by Toxoplasma gondii, a phenomenon termed fatal attraction, is interpreted as an adaptive manipulation by the neurotropic protozoan parasite. With the aim of understanding how the parasite induces such specific behavioral modifications, we performed a multiparametric analysis of T. gondii-induced changes on host behavior, physiology, and brain transcriptome as well as parasite cyst load and distribution. Using a set of complementary behavioral tests, we provide strong evidence that T. gondii lowers general anxiety in infected mice, increases explorative behaviors, and surprisingly alters predator aversion without selectivity toward felids. Furthermore, we show a positive correlation between the severity of the behavioral alterations and the cyst load, which indirectly reflects the level of inflammation during brain colonization. Taken together, these findings refute the myth of a selective loss of cat fear in T. gondii-infected mice and point toward widespread immune-related alterations of behaviors. : Contradicting the prevailing model of a selective loss of cat fear in Toxoplasma gondii-infected rodents, Boillat et al. show in a multiparametric analysis of host behavior, physiology, and brain transcriptome that the loss of predator fear is not specific to felids and that the severity of behavioral alterations correlates with neuroinflammation. Keywords: Apicomplexa, Toxoplasma gondii, parasites, chronic infection, host-pathogen interaction, effector molecules, innate behavior, predator avoidance, light-sheet microscopy, cat