Toxoplasma gondii promotes microRNA-34a to inhibit Foxp3 expression in adverse outcomes of pregnancy in mice

Abstract

Infection with Toxoplasma gondii (T. gondii) during the pregnant period causes microcephaly, mental and psychomotor retardation or death. Miserable outcomes are mainly linked with regulatory T cells (Tregs) dysfunction. Forkhead box P3 (Foxp3), a vital regulator of establishment and maintenance of Tregs, can be modulated by microRNAs (miRNAs). Previously, our study revealed that T. gondii infection in pregnant mice induced Tregs dysfunction, accompanied with reduced Foxp3 expression. The role of miRNAs in the inhibition of Foxp3 triggered by T. gondii remains unclear. Herein, T. gondii infection promotes miR-34a expression in the placenta of mice. miR-34a mimic inhibits Foxp3 expression via targeting 3′ untranslated region (3′UTR) whereas its inhibitor promotes Foxp3 expression in vitro. T. gondii antigens could enhance the activity of miR-34a promoter via a Smad4-dependent mechanism. Collectively, our data reveal a new avenue through which T. gondii inhibits Foxp3 expression necessary to drive adverse outcomes of pregnancy in mice.