Cutting Edge: Critical Roles for Microbiota-Mediated Regulation of the Immune System in a Prenatal Immune Activation Model of Autism

• Published in: The Journal of immunology (1950) Vol. 201; no. 3; pp. 845 - 850
• Main Authors: Lammert, Catherine R, Frost, Elizabeth L, Bolte, Ashley C, Paysour, Matt J, Shaw, Mariah E, Bellinger, Calli E, Weigel, Thaddeus K, Zunder, Eli R, Lukens, John R
• Format: Journal Article
• Language: English
• Published: United States American Association of Immunologists 01-08-2018
• Subjects: Activation; Animals; Autism; Autistic Disorder - immunology; Autistic Disorder - microbiology; Calibration; Disease Models, Animal; Female; Genetic crosses; Immune response; Immune System - immunology; Immunomodulation; Interleukin-17 - immunology; Landscape; Male; Mice; Mice, Inbred C57BL; Microbiomes; Microbiota; Microbiota - immunology; Microflora; Neurodevelopmental disorders; Offspring; Pathogenesis; Poly I-C - immunology; Polyinosinic:polycytidylic acid; Pregnancy; Prenatal Exposure Delayed Effects - immunology; Prenatal Exposure Delayed Effects - microbiology; Transplantation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1701755

Recent studies suggest that autism is often associated with dysregulated immune responses and altered microbiota composition. This has led to growing speculation about potential roles for hyperactive immune responses and the microbiome in autism. Yet how microbiome-immune cross-talk contributes to neurodevelopmental disorders currently remains poorly understood. In this study, we report critical roles for prenatal microbiota composition in the development of behavioral abnormalities in a murine maternal immune activation (MIA) model of autism that is driven by the viral mimetic polyinosinic-polycytidylic acid. We show that preconception microbiota transplantation can transfer susceptibility to MIA-associated neurodevelopmental disease and that this is associated with modulation of the maternal immune response. Furthermore, we find that ablation of IL-17a signaling provides protection against the development of neurodevelopmental abnormalities in MIA offspring. Our findings suggest that microbiota landscape can influence MIA-induced neurodevelopmental disease pathogenesis and that this occurs as a result of microflora-associated calibration of gestational IL-17a responses.