We are pleased to announce that our second CPIC Pilot Award recipient is Craig Bierle, PhD, an assistant professor at the University of Minnesota in the Department of Pediatrics, Division of Infectious Diseases. He will work with Mark Schleiss, MD, on his project entitled “T cells and cytomegalovirus-associated immunopathology.”
Dr. Bierle’s CPIC funding will allow him to understand how human cytomegalovirus (HCMV) infects the placenta. These infections can disrupt normal placental development and function, causing fetal growth restriction or, in severe cases, demise. His pilot research is assessing the role of the maternal and fetal T cell response to placental infection in adverse pregnancy outcomes.
Dr. Bierle recently found that GPCMV infection at this time causes a transcriptional response in placenta that is indicative of immune activation. As CXCL10 and IDO1 expression is upregulated in both HCMV- and GPCMV-infected placentas, he hypothesized that T cell infiltration causes placental dysfunction after viral infection. The CPIC pilot project is assessing how CD4+ and CD8+ T cell depletion affects the maternal and fetal immune response during GPCMV-infected and normal pregnancies.
In experiments supported by a pilot grant from the University of Minnesota Department of Pediatrics, Dr. Bierle is quantifying T cell abundance and localization in the placenta and fetus using a combination of flow cytometry and in situ hybridization. They are also assessing how T cell depletion affects the rate of fetal and placental infection.
Support from the CPIC pilot award is being used to extend this project to include analyses of T cell specificity towards viral and paternal antigens. Dr. Bierle is comparing the utility of enzyme-linked immunospot and intracellular flow cytometry assays for measuring antigen specific T cell responses. Additionally, he will develop next-generation sequencing methods to study T cell receptor diversity.
As maternal anti-fetal immune responses can compromise placental function in humans and mice, these experiments will provide data as to whether placental CMV infection disrupts maternal tolerance. These experiments will also determine whether antiviral T cell response is developed during fetal life. Successful completion of this project will inform how the immune response to congenital viral infection can injure the placenta.
The Congenital and Perinatal Infections Consortium (CPIC) is part of the Rare Diseases Clinical Research Network (RDCRN), which is funded by the National Institutes of Health (NIH) and led by the National Center for Advancing Translational Sciences (NCATS) through its Division of Rare Diseases Research Innovation (DRDRI). CPIC is funded under grant number U54AI150225 as a collaboration between NCATS and the National Institute of Allergy and Infectious Diseases (NIAID).