Abstract
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.
Footnotes
This work was supported by The Hartwell Foundation (Individual Biomedical Research Award to J.R.L.), the Owens Family Foundation (to J.R.L.), and The Simons Foundation Autism Research Initiative (Pilot Award 515305 to J.R.L. and E.R.Z.). C.R.L. was supported by a National Institutes of Health/National Institute of General Medical Sciences predoctoral training grant (3T32GM008328), A.C.B. was supported by the Medical Scientist Training Program at the University of Virginia (Grant 5T32GM007267-38), and C.E.B. was supported by Hutcheson and Stull Undergraduate Research Fellowships.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- ASD
- autism spectrum disorder
- Co Jax
- cohoused Jax
- E
- embryonic day
- Jax
- The Jackson Laboratory
- MIA
- maternal immune activation
- PolyI:C
- polyinosinic-polycytidylic acid
- SFB
- segmented filamentous bacteria
- Tac
- Taconic Biosciences
- USV
- ultrasonic vocalization.
- Received December 21, 2017.
- Accepted June 8, 2018.
- Copyright © 2018 by The American Association of Immunologists, Inc.