Maternal gastrointestinal nematode infection alters hippocampal neuroimmunity, promotes synaptic plasticity, and improves resistance to direct infection in offspring.

Author:

Noel Sophia C.1,Madranges Jeanne F.2,Gothié Jean-David M.2,Ewald Jessica1,Milnerwood Austen J.2,Kennedy Timothy E.2,Scott Marilyn E.1

Affiliation:

1. McGill University Institute of Parasitology

2. Montreal Neurological Institute and Hospital

Abstract

Abstract

The developing brain is vulnerable to maternal bacterial and viral infection which induce strong inflammatory responses in the mother that are mimicked in the offspring brain, resulting in irreversible neurodevelopmental defects, and associated cognitive and behavioural impairments. In contrast, maternal infection with the immunoregulatory murine intestinal nematode, Heligmosomoides bakeri, upregulates expression of genes associated with long-term potentiation (LTP) of synaptic networks in the brain of neonatal uninfected offspring, and enhances spatial memory in uninfected juvenile offspring. As the hippocampus is involved in spatial navigation and sensitive to immune events during development, here we assessed hippocampal gene expression, LTP, and neuroimmunity in three-week-old uninfected offspring born to H. bakeri infected mothers. Further, as maternal immunity shapes the developing immune system, we assessed the impact of maternal H. bakeri infection on the ability of offspring to resist direct infection. In response to maternal infection, we found an enhanced propensity to induce LTP, consistent with RNA-seq data indicating accelerated development of glutamatergic synapses in offspring, relative to those from uninfected mothers. Hippocampal RNA-seq analysis of offspring of infected mothers revealed increased expression of genes associated with neurogenesis, gliogenesis, and myelination. Furthermore, maternal infection improved resistance to direct infection of H. bakeri in offspring, correlated with transfer of parasite-specific IgG1 to their serum. Hippocampal immunohistochemistry and gene expression suggest Th2/Treg biased neuroimmunity in offspring, recapitulating peripheral immunoregulation of H. bakeri infected mothers. These findings indicate maternal H. bakeri infection alters peripheral and neural immunity and hippocampal gene expression in uninfected offspring, in a manner that accelerates neural maturation to promote hippocampal LTP, neurogenesis, gliogenesis, and myelination.

Publisher

Research Square Platform LLC

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