Bacterial-induced maternal interleukin-17A pathway promotes autistic-like behaviors in mouse offspring

• Published in: Experimental Animals 2020, Vol.69(2), pp.250-260
• Main Authors: Yasumatsu, Kanae, Nagao, Jun-ichi, Arita-Morioka, Ken-ichi, Narita, Yuka, Tasaki, Sonoko, Toyoda, Keita, Ito, Shoko, Kido, Hirofumi, Tanaka, Yoshihiko
• Format: Article
• Language: English
• Subjects: Animal models; Autism; autism spectrum disorder (ASD); Bacteria; Bacterial diseases; Bacterial infections; Brain; Environmental factors; Fetuses; Gene expression; IL-17A; Immune response; Immune system; immunology; Infections; Interleukin 1; Interleukins; lipopolysaccharide (LPS); Lipopolysaccharides; Lymphocytes; Lymphocytes T; Maternal behavior; maternal immune activation (MIA); Offspring; Original; Uterus
• ISSN: 1341-1357; 1881-7122
• DOI: 10.1538/expanim.19-0156

Maternal immune activation (MIA) by an infection is considered to be an important environmental factor of fetal brain development. Recent animal model on MIA induced by polyinosinic:polycytidylic acid, a mimic of viral infection, demonstrates that maternal IL-17A signaling is required for the development of autism spectrum disorder (ASD)-like behaviors of offspring. However, there is little information on bacterial infection. In this study, we aim to elucidate the influence of MIA induced by lipopolysaccharide (LPS) to mimic a bacterial infection on fetal brain development. We demonstrated that LPS-induced MIA promoted ASD-like behaviors in mouse offspring. We further found that LPS exposure induced acute phase immune response: elevation of serum IL-17A levels in MIA mothers, upregulation of Il17a mRNA expression and increase of IL-17A-producing γδ T cells in the uterus, and upregulation of Il17ra mRNA expression in the fetal brain. Blocking of IL-17A in LPS-induced MIA ameliorated ASD-like behaviors in offspring. Our data suggest that bacterial-induced maternal IL-17A pathway promotes ASD-like behaviors in offspring.