Characterization of susceptibilities and assessment of risk to Listeria monocytogenes exposure in pregnant guinea pigs and primates
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Pre-term delivery of a stillborn or neonatal illness can result from exposure of a pregnant woman to Listeria monocytogenes. The objectives of this research are to use our previously established guinea pig model to 1) conduct a risk assessment of L. monocytogenes using dose-response data from primate and guinea pig models and compare the results to previous assessments 2) investigate invasion of L. monocytogenes in tissues at various intervals following maternal ingestion using culturing and microscopy 3) investigate the impact of gestation and dose on tissue invasion with L. monocytogenes, fecal shedding and birth outcome and 4) determine whether exposure induces changes in select pro-inflammatory and anti-inflammatory cytokine mRNA expression in fetal liver and brain. We evaluated risk based on dose-responses from pregnant rhesus monkeys and guinea pigs. The mortality rate was calculated using new dose-response information, and results show that the mortality rate of 5.9x101 using primates is much different from the predicted rate of 1.3x10-7 by the FDA/USDA/CDC. To determine a time course of tissue invasion, guinea pigs were sacrificed on post treatment days (ptd) 2, 6, 9 and 21. Maternal and fetal tissues were invaded at 2 days post treatment. At the highest administered dose of 108 cfu the average time to stillbirth was 10 ptd indicating that it takes several days for listeriosis to progress and kill the fetus. Independently, culturing and microscopy may underestimate the number of positive samples but combined can be effective tools for confirmation of L. monocytogenes. When addressing whether gestation and dose affected tissue invasion and fecal shedding following L. monocytogenes exposure we found that non-pregnant animals are invaded after L. monocytogenes exposure and the likelihood of invasion and shedding is dose dependent. Earlier gestation did not reduce or prevent the risk for tissue invasion or fetal death. At the dose of 102 CFU, TNF-α and IL-2 were decreased in fetal brain and liver. At 107 CFU, all cytokines were decreased in the fetal brain. However, in the fetal liver, IFN-γ, TNF-α and IL-5 were increased with IL-2 at lower levels compared to controls.