To be or not to be: how does the brain respond to different infectious agents?

Toxoplasma gondii is an apicomplexan parasite that chronically infects approximately 30% of the global population. In healthy adults, infection is typically resolved within a few weeks, resulting in tissue cysts that persist in the central nervous system for the lifetime of the host. In immune-compromised patients, infection can manifest as toxoplasmic encephalitis and blindness. Additionally, there are several neurological and psychiatric associations with toxoplasmosis, including but not limited to epilepsy and bipolar disorder. This commentary reflects on recent work by Johnson and colleagues (H. J. Johnson, J. A. Kochanowsky, S. Chandrasekaran, C. A. Hunter, et al., mSphere 10:e00216-25, 2025, https://doi.org/10.1128/msphere.00216-25) investigating the difference in neuronal response to T. gondii compared to neurotropic West Nile and Zika viruses. They identify unique neurological and immune signatures associated with the different infections, as well as overlapping pathways enriched regardless of pathogen type. This study provides insights into host signaling pathways that can be manipulated for therapies against toxoplasmosis.