Neonatal infection with Bordetella pertussis promotes autism-like phenotypes in mice
Eoin O’Neill,
Lucy Curham,
Caitlín Ní Chasaide,
Síofra O’Brien,
Gavin McManus,
Barry Moran,
Keith Rubin,
Steven Glazer,
Marina A. Lynch,
Kingston H.G. Mills
Affiliations
Eoin O’Neill
Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02R590 Dublin, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, D02PD91 Dublin, Ireland
Lucy Curham
Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02R590 Dublin, Ireland
Caitlín Ní Chasaide
Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02R590 Dublin, Ireland
Síofra O’Brien
Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02R590 Dublin, Ireland
Gavin McManus
Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02R590 Dublin, Ireland
Barry Moran
Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02R590 Dublin, Ireland
Keith Rubin
ILiAD Biotechnologies, Weston, FL 33331, USA
Steven Glazer
ILiAD Biotechnologies, Weston, FL 33331, USA
Marina A. Lynch
Trinity College Institute of Neuroscience, Trinity College Dublin, D02PD91 Dublin, Ireland
Kingston H.G. Mills
Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, D02R590 Dublin, Ireland; Corresponding author
Summary: Autism spectrum disorder (ASD) has been linked with infections early in life. Here we demonstrate that the infection of neonatal mice with the respiratory pathogen Bordetella pertussis leads to neuroinflammation, neurodevelopmental defects, and ASD-like behaviors. Following the respiratory challenge of neonatal mice with B. pertussis, multiple atypical CNS findings were observed, including blood-brain barrier disruption, dissemination of live B. pertussis bacteria to the brain with the concomitant infiltration of inflammatory monocytes, neutrophils, and activated IL-17A- and IFN-γ-producing CD4 T cells. Microglia from infected mice were activated, with impaired phagocytic function, resulting in defective synaptic pruning and disrupted neuronal circuit formation. Impaired neurodevelopment in B. pertussis-infected post-natal mice was associated with ASD-like behavioral abnormalities in young adulthood. Our data indicate that infection with virulent B. pertussis during infancy increases the risk of autism-like behavior in young adult mice. A study into the potential role of B. pertussis in human ASD is warranted.
