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Nature. 2017 Sep 28;549(7673):528-532. doi: 10.1038/nature23910. Epub 2017 Sep 13.

Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring.

Author information

1
Division of Infectious Diseases and Immunology and Program in Innate Immunity, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
2
The McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
3
Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.
4
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
5
The Jill Roberts Institute for Research in IBD, Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York 10021, USA.
6
The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA.
7
Howard Hughes Medical Institute, New York, New York 10016, USA.

Abstract

Maternal immune activation (MIA) contributes to behavioural abnormalities associated with neurodevelopmental disorders in both primate and rodent offspring. In humans, epidemiological studies suggest that exposure of fetuses to maternal inflammation increases the likelihood of developing autism spectrum disorder. In pregnant mice, interleukin-17a (IL-17a) produced by T helper 17 (TH17) cells (CD4+ T helper effector cells involved in multiple inflammatory conditions) induces behavioural and cortical abnormalities in the offspring exposed to MIA. However, it is unclear whether other maternal factors are required to promote MIA-associated phenotypes. Moreover, the underlying mechanisms by which MIA leads to T cell activation with increased IL-17a in the maternal circulation are not well understood. Here we show that MIA phenotypes in offspring require maternal intestinal bacteria that promote TH17 cell differentiation. Pregnant mice that had been colonized with mouse commensal segmented filamentous bacteria or human commensal bacteria that induce intestinal TH17 cells were more likely to produce offspring with MIA-associated abnormalities. We also show that small intestine dendritic cells from pregnant, but not from non-pregnant, females secrete IL-1β, IL-23 and IL-6 and stimulate T cells to produce IL-17a upon exposure to MIA. Overall, our data suggest that defined gut commensal bacteria with a propensity to induce TH17 cells may increase the risk of neurodevelopmental disorders in the offspring of pregnant mothers undergoing immune system activation owing to infections or autoinflammatory syndromes.

PMID:
28902840
PMCID:
PMC5870873
DOI:
10.1038/nature23910
[Indexed for MEDLINE]
Free PMC Article

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