Exosome trafficking from the placenta into the maternal circulation is well documented; the possibility that this trafficking is bi‐directional was unknown. We demonstrated clathrin‐mediated endocytosis of macrophage exosomes by the human placenta. We also demonstrated that macrophage exosomes induced placental production of cytokines interleukin (IL)‐6, IL‐8 and IL‐10. Exosomes therefore comprise an additional mechanism of immune cell signalling to the placenta, potentially facilitating protective responses to maternal inflammation and infection in pregnancy. This represents a novel mode of maternal–placental messaging.

No abstract

Herpes simplex encephalitis is a rare manifestation of herpes simplex virus-1 infection. Mutations in genes of the toll-like receptor 3-interferon pathway have been shown to predispose to childhood herpes simplex encephalitis, including UNC93B1, TLR3, TRIF, TRAF3 and TBK1. We investigated herpes simplex encephalitis patients with impaired toll-like receptor 3 signaling for whom the involvement of the known genetic etiologies have been excluded. Exome sequencing was used to identify other mutations underlying herpes simplex encephalitis, paying particular attention to the toll-like receptor 3-interferon pathway by employing a candidate gene based ‘connectome’ approach. One patient in particular carried a novel heterozygous missense mutation in a known gene in the nuclear factor-κB / toll-like receptor 3 pathway. The patient’s cells showed a decrease in interferon regulatory factor-3 dimerization and reduced nuclear translocation of nuclear factor-κB consistent with the lack of type I interferon and IL6 production following toll-like receptor 3 stimulation. The patients’ cells were also more susceptible upon viral infections. Further characterization of the mutation and its impact on type I interferon signaling in the context of herpes simplex virus-1 infection will provide a better understanding of the etiology of childhood herpes simplex encephalitis.