Rescue of maternal immune activation-induced behavioral abnormalities in adult mouse offspring by pathogen-activated maternal Treg 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. Xu et al. developed and characterized a new animal model of maternal immune activation based on a parasite mimetic. They show that immune and behavioral abnormalities in adult offspring are reversed by adoptive transfer of regulatory T cells.