Abstract
ABSTRACTInfection with Listeria monocytogenes during pregnancy is associated with miscarriage, preterm birth, and neonatal complications, including sepsis and meningitis. While the risk of these conditions is thought to be greatest during the third trimester of pregnancy, the determinants of fetoplacental susceptibility to infection, the contribution of gestational age, and the in vivo progression of disease at the maternal-fetal interface are poorly understood. We developed a nonhuman primate model of listeriosis to better understand antecedents of adverse pregnancy outcomes in early pregnancy. Four pregnant cynomolgus macaques (Macaca fascicularis) received a single intragastric inoculation between days 36 and 46 of gestation with 107 CFU of an L. monocytogenes strain isolated from a previous cluster of human listeriosis cases that resulted in adverse pregnancy outcomes. Fecal shedding, maternal bacteremia, and fetal demise were consistently noted within 7 to 13 days. Biopsy specimens of maternal liver, spleen, and lymph node displayed variable inflammation and relatively low bacterial burden. In comparison, we observed greater bacterial burden in the decidua and placenta and the highest burden in fetal tissues. Histopathology indicated vasculitis, fibrinoid necrosis, and thrombosis of the decidual spiral arteries, acute chorioamnionitis and villitis in the placenta, and hematogenous infection of the fetus. Vascular pathology suggests early impact of L. monocytogenes infection on spiral arteries in the decidua, which we hypothesize precipitates subsequent placentitis and fetal demise. These results demonstrate that L. monocytogenes tropism for the maternal reproductive tract results in infection of the decidua, placenta, and the fetus itself during the first trimester of pregnancy.
Highlights
IMPORTANCE listeriosis is known to cause significant fetal morbidity and mortality, it is typically recognized in the third trimester of human pregnancy
Each animal received ~107 CFU of L. monocytogenes in 10 ml of whipping cream through a soft intragastric feeding tube while under sedation. This strain of L. monocytogenes was associated with a listeriosis outbreak that resulted in adverse pregnancy outcomes in 11 pregnant women [7]
While it is recognized that adverse pregnancy outcomes associated with maternal listeriosis typically include placental infection, the precise pathogenesis of placental infection and subsequent fetal infection remains incompletely described
Summary
IMPORTANCE listeriosis is known to cause significant fetal morbidity and mortality, it is typically recognized in the third trimester of human pregnancy. We highlight the concept that the maternal immune response that protects the mother from serious disease is unable to protect the fetus, a concept relevant to classic TORCH (toxoplasmosis, other, rubella, cytomegalovirus, and herpes) infections and newly illuminated by current Zika virus outbreaks Studies with this model, using the well-understood organism L. monocytogenes, will permit precise. Macaques and other nonhuman primates have villous hemochorial placentas and invasive extravillous fetal trophoblasts that actively remodel maternal spiral arteries in the decidua Their similar endocrine, reproductive, and immune systems make nonhuman primates a highly relevant model for examining the interplay of maternal and fetal responses to infection during pregnancy. Microbial analysis of collected tissues revealed that the decidua basalis and placental bed as well as the placenta had significant bacterial burden These findings suggest that maternal infection affects both the placenta—the presumptive target of listeriosis during human pregnancy—and the maternal reproductive tract
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