Evaluation of Novel Interferon Epsilon across Human Pregnancy
Grant
Overview
Affiliation
Other
View All
Overview
abstract
Reproductive and pregnancy complications are prevalent, are often recurrent and have poorlyunderstood etiologies. There is mounting evidence that innate immune factors are important forreproductive immune homeostasis to support fertilization, implantation, placentation and overallpregnancy health while maintaining protection against pathogens. This is significant as sexuallytransmitted infections (STIs), which lead to adverse reproductive and pregnancy outcomes, arecurrently at an exceptional high in the United States. Furthermore, infection-related pregnancyoutcomes, such as preterm birth, occur at the same rate in the U.S. as some middle and low-income countries (11%), particularly in minority populations. Even in the absence of STIs, thegenital microbiome may have a significant influence on reproductive immunology. Thus,immune molecules may be targets for novel therapies to improve reproductive and pregnancyhealth. Recently characterized type I interferon epsilon (IFNe) has been reported in animal andexperimental models to maintain reproductive tract IFN-stimulated gene expression and form aninnate immune defense against STIs. Indeed, studies suggest that IFNe is a potential novelmucosal therapeutic against genital infections. However, the role of IFNe in human reproductivesuccess is not elucidated. There is a critical need to increase the understanding of theepidemiology, biology and clinical utility of IFNe. Pregnancy is a dynamic immunological stateand other type I IFNs, such as IFN-beta, modulate maternal immunity, promote tolerance to thefetus and protect against pathogens. However, type I IFNs can also exacerbate disease,particularly following bacterial infections. This is likely due to increased signaling by the innateimmune receptors that regulate IFN expression. However, IFNe is unique as it is regulated byreproductive hormones which makes this type I IFN a more desirable target for mucosaltherapeutics. A pilot investigation of 25 pregnant women showed that IFNe is present in thelower genital tract, increases as gestation progresses and is lower in pregnant women withgenital infections and high body mass index. The objective of this R21 proposal is to 1) validateprior estimates of vaginal IFNe expression across pregnancy; 2) identify maternal demographiccharacteristics that influence IFNe levels and 3) determine if lower IFNe levels are associatedwith maternal and infant health indicators. This study is innovative as it will be the firstlongitudinal investigation of human IFNe in pregnancy. Data generated from this study will beused for future investigations to determine if IFNe has any clinical utility in protection againstgenital tract infections and improves reproductive and pregnancy success.
