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

Nat Neurosci. 2021 Jun;24(6):818-830. doi: 10.1038/s41593-021-00837-1. Epub 2021 Apr 15.

Abstract

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 (Treg) cells largely reversed these MIA-induced phenotypes. Notably, pathogen-activated maternal Treg cells showed greater rescue efficacy than those from control donors. Single-cell RNA sequencing identified and characterized a unique group of pathogen-activated Treg cells that constitute 32.6% of the pathogen-activated maternal Treg population. Our study establishes a new preclinical parasite-mimicking MIA model and suggests therapeutic potential of adoptive Treg cell transfer in neuropsychiatric disorders associated with immune alterations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods
  • Animals
  • Antigens, Protozoan / administration & dosage
  • Antigens, Protozoan / toxicity*
  • Female
  • HeLa Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pregnancy
  • Prenatal Exposure Delayed Effects / immunology*
  • Prenatal Exposure Delayed Effects / parasitology*
  • Social Interaction*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / parasitology*
  • Vocalization, Animal / physiology

Substances

  • Antigens, Protozoan
  • soluble tachyzoite antigen, Toxoplasma gondii