Project description:Decidual NK cells (dNK) are key immune effector cells at the maternal-fetal interface. dNK utilize the anti-microbial peptide granulysin (GNLY) to kill pathogens, without killing trophoblast cells. Since rodents lack the GNLY gene, the in vivo biology of GNLY expression by dNK and their control of microbes is not well-understood. Here we defined dNK GNLY expression in placental membranes of Rhesus macaques and humans. GNLY-high dNK of both species shared conserved transcriptional and protein signatures of anti-microbial defense and immunoregulation. In addition, both human and rhesus GNLY-high dNK responded to inflammation and infection by increasing their cytotoxic, cytokine and inflammatory signatures. Thus high GNLY expression defines a unique dNK type with active roles in innate immune defense in humans and Rhesus macaques. Defining the regulatory networks of GNLY expression by dNK and their mechanism of infection control will open up therapeutic opportunities to enhance immunity and reduce infection-related pregnancy complications
Project description:A Toxoplasma gondii infection during pregnancy can result in spontaneous abortion, preterm labor, or congenital fetal defects. The decidual immune system plays a critical role in regulating the immune micro-environment and in the induction of immune tolerance. To better understand the factors that mediate the decidual immune response associated with the T. gondii infection, a large-scale study employing TMT proteomics was conducted to characterize the differential decidual immune proteomes from infected and uninfected human decidual immune cells samples. The decidual immune cells from 105 human voluntary abortion tissues were purified, and of the 5510 unique proteins identified, 181 proteins were found to be differentially abundant (>1.2-fold cutoff, P<0.05) in the T. gondii-infected decidual immune cells. 11 proteins of 181 differentially expressed proteins associated with trophoblast invasion, placental development, intrauterine fetal growth, and immune tolerance were verified using a quantitative real-time polymerase chain reaction and western blotting. This systematic research identified a broad range of immune factors in human decidual immune cells, shedding a new insight into the decidual immune molecular mechanism for abnormal pregnancy outcomes associated with T. gondii infection.
Project description:Congenital cytomegalovirus (cCMV) is the most common intrauterine infection, leading to infant neurodevelopmental disabilities. An improved knowledge of correlates of protection against cCMV is needed to guide prevention strategies. Here, we employed a unique ex vivo model of human CMV (HCMV) infection in decidual tissues of women with and without preconception immunity, recapitulating nonprimary versus primary infection at the authentic maternofetal transmission site. We showed that decidual tissues of women with preconception immunity exhibited intrinsic resistance to HCMV, mounting a rapid activation of tissue resident memory CD8+ and CD4+ T cells upon nonprimary infection. We further revealed the role of HCMV-specific decidual-tissue resident CD8+ T cells in local protection against nonprimary HCMV infection. The findings could inform the development of vaccine against cCMV, and provide insights for further studies of the integrity of immune defense against cCMV and other pathogens in the human maternal-fetal interface.
Project description:Genome-wide prefrontal cortex and cerebellum DNA methylation profiles of younger and older adult humans, captive chimpanzees, and captive rhesus macaques
Project description:Decidual macrophage populations, CD11cHI and CD11cLO cells were analyzed for expression profiles and unique characteristics. We used microarrays to detail the global program of gene expression and to determine differences between these two unique decidual macrophage populations.
Project description:A successful pregnancy requires many physiological adaptations from the mother, including the establishment of tolerance towards the semiallogeneic fetus. Innate lymphoid cells (ILCs) have arisen as important players in immune regulation and tissue homeostasis at mucosal and barrier surfaces. Dimensionality reduction and transcriptomic analysis revealed the presence of two novel CD56Bright decidual ILCs, C10 and C2, that express divergent levels of Eomes. We found that decidual C10, C2, and cNKs correlated highly with previously identified first trimester decidual dNKs (dNK1-3). Functional analysis revealed polyfunctional profiles that depend on the nature of the stimulus, with a preference for IFNgamma and VEGF production. Overall, our data suggests persistence of pregnancy-specific decidual innate lymphocytes across pregnancy.
Project description:Transcriptional profiling of cynomolgus macaques liver tissue comparing control young macaques with elder macaques. Goal was to determine the liver genetic change with aging of macaques.