Exposure to pesticides in utero impacts the fetal immune system and response to vaccination in infancy
Mary Prahl, Pamela M. Odorizzi, David Gingrich, Mary Muhindo, Tara I. McIntyre, Rachel Budker, Prasanna Jagannathan, Lila A. Farrington, Mayimuna Nalubega, Felistas Nankya, Esther Sikyomu, Kenneth Musinguzi, Kate Naluwu, Ann Auma, Abel Kakuru, Moses R. Kamya, Grant Dorsey, Francesca Aweeka, Margaret E. Feeney
Abstract
The use of pesticides to reduce mosquito vector populations is a cornerstone of global malaria control efforts, but the biological impact of most pesticides on human populations, including pregnant women and infants, is not known. Some pesticides, including carbamates, have been shown to perturb the human immune system. We measure the systemic absorption and immunologic effects of bendiocarb, a commonly used carbamate pesticide, following household spraying in a cohort of pregnant Ugandan women and their infants. We find that bendiocarb is present at high levels in maternal, umbilical cord, and infant plasma of individuals exposed during pregnancy, indicating that it is systemically absorbed and trans-placentally transferred to the fetus. Moreover, bendiocarb exposure is associated with numerous changes in fetal immune cell homeostasis and function, including a dose-dependent decrease in regulatory CD4 T cells, increased cytokine production, and inhibition of antigen-driven proliferation. Additionally, prenatal bendiocarb exposure is associated with higher post-vaccination measles titers at one year of age, suggesting that its impact on functional immunity may persist for many months after birth. These data indicate that in utero bendiocarb exposure has multiple previously unrecognized biological effects on the fetal immune system.