Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal T reg cells

Maternal immune activation (MIA) induced by lipopolysaccharides or polyinosinic:polycytidylic acid injections can induce behavioral abnormalities in adult mouse offspring. Here, we used the soluble tachyzoite antigen from Toxoplasma gondii , a parasite that infects approximately two billion people, to induce MIA in mice. The adult male offspring showed autism-relevant behaviors and abnormal brain microstructure, along with a pro-inflammatory T-cell immune profile in the periphery and upregulation of interleukin-6 in brain astrocytes. We show that adoptive transfer of regulatory T (T reg ) cells largely reversed these MIA-induced phenotypes. Notably, pathogen-activated maternal T reg cells showed greater rescue efficacy than those from control donors. Single-cell RNA sequencing identified and characterized a unique group of pathogen-activated T reg cells that constitute 32.6% of the pathogen-activated maternal T reg population. Our study establishes a new preclinical parasite-mimicking MIA model and suggests therapeutic potential of adoptive T reg cell transfer in neuropsychiatric disorders associated with immune alterations.