Vertical transmission of Leishmania donovani with placental degeneration in the pregnant mouse model of visceral leishmaniasis.

Abstract

Visceral leishmaniasis (VL) is a zoonotic disease caused by infection of macrophages by Leishmania donovani or L. infantum, and exhibits symptoms such as fever, anemia, and hepatosplenomegaly. VL during pregnancy has been reported to have negative effects such as miscarriage and vertical infection, but the mechanism is not clear. Here, we aimed to establish a pregnant VL mouse model and elucidate its immunopathology. Female BALB/c mice mated 6 months after L. donovani infection showed reduced pregnancy rates. The fetus was removed by caesarean section on the 18th day of pregnancy, and Leishmania parasite DNA was detected from fetal spleens and livers. As a result, the PCR positive rate was 68.9% (71/103 fetus), and vertical transmission was suspected in 66.7% of infected mothers (12/18 dams). Immunohistochemistry in the fetal livers detected cells positive for the Leishmania antigen, kinetoplastid membrane protein 11 (KMP11). In addition, pathological analysis of the VL placenta revealed trophoblast cell atrophy and vasodilation accompanied by CD3+ cell infiltration in the infected group. On the other hand, few KMP11+ cells were observed in the placenta of the infected group. Furthermore, RNA-Seq analysis revealed that IFN signal activation and cellular immune suppression were induced in the placenta of the infected group. These results suggest that VL in pregnancy induces suppression of placental cellular immunity through IFN and collapse of the placental barrier through trophoblast degeneration, leading to vertical transmission. Because few infected macrophages were observed in the placenta, it is possible that free Leishmania parasites in the blood contribute to transmission across the placenta.