Neonatal infection with Bordetella pertussis promotes autism-like phenotypes in mice

Autism spectrum disorder (ASD) has been linked with infections early in
life. Here we demonstrate that infection of neonatal mice with the
respiratory pathogen Bordetella pertussis leads to neuroinflammation,
neurodevelopmental defects and ASD-like behaviours. Following 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 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 behavioural abnormalities in young adulthood. Our data
indicate that infection with virulent B. pertussis during infancy
increases the risk of autism-like behaviour in young adult mice. Study
into the potential role of B. pertussis in human ASD is warranted.