Title | Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Kim S, Kim H, Yim YShin, Ha S, Atarashi K, Tan TGuan, Longman RS, Honda K, Littman DR, Choi GB, Huh JR |
Journal | Nature |
Volume | 549 |
Issue | 7673 |
Pagination | 528-532 |
Date Published | 2017 09 28 |
ISSN | 1476-4687 |
Keywords | Animals, Behavior, Animal, Dendritic Cells, Female, Gastrointestinal Microbiome, Inflammation, Interleukin-17, Interleukin-1beta, Interleukin-23, Interleukin-6, Intestine, Small, Male, Mice, Phenotype, Pregnancy, Prenatal Exposure Delayed Effects, Symbiosis, Th17 Cells |
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 (T17) 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 T17 cell differentiation. Pregnant mice that had been colonized with mouse commensal segmented filamentous bacteria or human commensal bacteria that induce intestinal T17 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 T17 cells may increase the risk of neurodevelopmental disorders in the offspring of pregnant mothers undergoing immune system activation owing to infections or autoinflammatory syndromes. |
DOI | 10.1038/nature23910 |
Alternate Journal | Nature |
PubMed ID | 28902840 |
PubMed Central ID | PMC5870873 |
Grant List | R01 DK106351 / DK / NIDDK NIH HHS / United States R01 DK110559 / DK / NIDDK NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States R01 MH106497 / MH / NIMH NIH HHS / United States R01 MH115037 / MH / NIMH NIH HHS / United States K08 DK099381 / DK / NIDDK NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:12pm