Physiological microbial exposure normalizes memory T cell surveillance of the brain and modifies host seizure outcomes

Abstract

Recent studies have highlighted the presence of memory T cells in human brains, some of which are specific for peripheral infections. To address their potential origins, we used two models of polymicrobial exposure to ‘normalize’ the immune systems of specific pathogen-free mice and queried the impact on brain T cell biology. Here, we show that cohousing and sequential infection induce marked enhancement of memory T cells in the brain tissue of mice. These resident and circulating memory T cells localized to diverse brain regions where dynamic interactions with myeloid cells occurred. Following an induced seizure, brain-localized memory T cells were functionally altered in microbe-experienced mice. Microbial exposure also induced T cell-dependent changes in seizure duration. These data not only suggest a potential origin for memory T cells in human brains but also reveal the ability of these cells to modulate brain biology, prompting the future utilization of microbe-experienced mice in studies of neurological health and disease.