Bacterial-induced maternal interleukin-17A pathway promotes autistic-like behaviors in mouse offspring. 2020

Kanae Yasumatsu, and Jun-Ichi Nagao, and Ken-Ichi Arita-Morioka, and Yuka Narita, and Sonoko Tasaki, and Keita Toyoda, and Shoko Ito, and Hirofumi Kido, and Yoshihiko Tanaka
Section of Infection Biology, Department of Functional Bioscience, Fukuoka Dental College, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.

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.

UI MeSH Term Description Entries
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001321 Autistic Disorder A disorder beginning in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual. (DSM-V) Autism, Infantile,Kanner's Syndrome,Autism,Autism, Early Infantile,Disorder, Autistic,Disorders, Autistic,Early Infantile Autism,Infantile Autism,Infantile Autism, Early,Kanner Syndrome,Kanners Syndrome
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D020381 Interleukin-17 A proinflammatory cytokine produced primarily by T-LYMPHOCYTES or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene. IL-17,CTLA-8,CTLA8,Cytokine CX2,Cytokine ML-1,Cytotoxic T lymphocyte-Associated Antigen 8,IL-17A,IL-17B,IL-17C,IL-17E,IL-17F,Interleukin 17,Interleukin-17A,Interleukin-17B,Interleukin-17C,Interleukin-17E,Interleukin-17F,Interleukin-25,CX2, Cytokine,Cytokine ML 1,Cytotoxic T lymphocyte Associated Antigen 8,IL 17E,Interleukin 17A,Interleukin 17B,Interleukin 17C,Interleukin 17E,Interleukin 17F,Interleukin 25

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