Programming Offspring Immunity By In Utero Exposure to Maternal Helminth Infection

PROJECT SUMMARY Millions of pregnant women worldwide harbor at least one type of parasite infection. In countries where helminth infections are prevalent in pregnant women, infants have reduced response to immunizations against multiple diseases. Helminth infections in pregnant mothers are implicated in this reduced vaccine efficacy in infants and children. However, very little is known about the factors that drive alterations in fetal immune programing and infant immune responses. The goal of this proposal is to fill this knowledge gap using a tractable experimental system in mice that we have developed. We leveraged our expertise in parasite-virus co-infection to establish a model of maternal helminth infection and our goal is to discover mechanisms that underly difference in fetal immune programming that occur with prenatal exposure to infections. We found that offspring exposed prenatally to maternal helminth infection have reduced susceptibility to influenza virus infection. We hypothesize that maternal helminth infection independent of in utero transmission alters immune programming in offspring through alterations to maternal and fetal microbiota. We will test this hypothesis with two aims. The first aim is to determine replication and inflammatory response to influenza virus in the lungs of offspring with and without prenatal helminth exposure. Because intestinal helminth infections change the microbiome of infected mice and the fetal microbiome is acquired from the nursing mother, the second aim is to determine the contribution of the helminth-altered microbiota to changes in offspring antiviral responses. At the completion of this study, we anticipate identifying immunological mechanisms underlying transgenerational imprinting of offspring immunity. Furthermore, this work will inform efforts to improve immune responses in children in helminth endemic areas to infection and vaccination.