Malaria-induced bacteremia as a consequence of multiple parasite survival strategies.

Globally, malaria continues to be an enormous public health burden, with concomitant parasite-induced damage to the gastrointestinal (GI) barrier resulting in bacteremia-associated morbidity and mortality in both adults and children. Infected red blood cells sequester in and can occlude the GI microvasculature, ultimately leading to disruption of the tight and adherens junctions that would normally serve as a physical barrier to translocating enteric bacteria. Mast cell (MC) activation and translocation to the GI during malaria intensifies damage to the physical barrier and weakens the immunological barrier through the release of enzymes and factors that alter the host response to escaped enteric bacteria. In this context, activated MCs release Th2 cytokines, promoting a balanced Th1/Th2 response that increases local and systemic allergic inflammation while protecting the host from overwhelming Th1-mediated immunopathology. Beyond the mammalian host, recent studies in both the lab and field have revealed an association between a Th2-skewed host response and success of parasite transmission to mosquitoes, biology that is evocative of parasite manipulation of the mammalian host. Collectively, these observations suggest that malaria-induced bacteremia may be, in part, an unintended consequence of a Th2-shifted host response that promotes parasite survival and transmission. Future directions of this work include defining the factors and mechanisms that precede the development of bacteremia, which will enable the development of biomarkers to simplify diagnostics, the identification of therapeutic targets to improve patient outcomes and better understanding of the consequences of clinical interventions to transmission blocking strategies.

Embryonic intraventricular exposure to autism-specific maternal autoantibodies produces alterations in autistic-like stereotypical behaviors in offspring mice.

Multiple studies have implicated a role of maternal autoantibodies reactive against fetal brain proteins specific to autism in the etiology of autism spectrum disorders (ASD). In the current study, we examined the impact of brain-reactive maternal autoantibodies of mothers of children with autism (MAU) on offspring behavior in mice compared to offspring exposed to non-reactive IgG of mothers of typically developing children (MTD). Embryonic offspring were exposed to a single intraventricular injection of MAU or MTD IgG on embryonic day 14. Offspring were allowed to mature to adulthood and were subsequently tested for sociability and stereotypic behaviors using a 3-chambered social approach task, marble burying task, and assessment of spontaneous grooming behaviors in response to a novel environment. Results indicate that MAU offspring display autistic-like stereotypical behavior in both marble burying and spontaneous grooming behaviors. Additionally, small alterations in social approach behavior were also observed in MAU offspring compared to MTD offspring. This report demonstrates for the first time the effects of a single, low dose intraventricular exposure of IgG derived from individual MAU samples on offspring behavior.