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

Autor:	Lammert CR; Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908.; Graduate Program in Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908., Frost EL; Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908., Bolte AC; Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908.; Medical Scientist Training Program, School of Medicine, University of Virginia, Charlottesville, VA 22908; and., Paysour MJ; Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908., Shaw ME; Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908., Bellinger CE; Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908., Weigel TK; Graduate Program in Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908., Zunder ER; Graduate Program in Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908.; Department of Biomedical Engineering, School of Engineering and Applied Science, University of Virginia, Charlottesville, VA 22908., Lukens JR; Center for Brain Immunology and Glia, Department of Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908; Jrl7n@virginia.edu.; Graduate Program in Neuroscience, School of Medicine, University of Virginia, Charlottesville, VA 22908.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2018 Aug 01; Vol. 201 (3), pp. 845-850. Date of Electronic Publication: 2018 Jul 02.
DOI:	10.4049/jimmunol.1701755
Abstrakt:	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. (Copyright © 2018 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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