Abstract
During pregnancy, immune cells infiltrate the placenta at different stages of fetal development. NK cells and macrophages are the most predominant cell types. These immune cells play pleiotropic roles, as they control spiral artery remodeling to ensure appropriate blood supply and maintain long-term tolerance to a true allograft; yet, they must be able to mount appropriate immune defenses to pathogens that may threaten the fetus. Whether the same cell type accomplishes all these tasks or if there are dedicated subsets remains controversial. Here, we identify and characterize two distinct subsets of myeloid cells that differ in their pro-inflammatory/regulatory capacity. While one subset predominantly produces the immune-modulating cytokine IL-10, the second subset has superior capacity to secrete pro-inflammatory mediators, such as IL-1β and IL-6. The putative regulatory myeloid cells also express high levels of inhibitory receptors and their ligands, including programmed cell death 1 (PD1) ligands. Importantly, a large fraction of CD8 and CD4 cells in normal term human placenta are PD1 positive, suggesting that the PD1/PD1 ligands axis might be critical to maintain tolerance during pregnancy.
Highlights
Pregnancy is a unique situation during which a truly hemi-allogeneic tissue is well protected from the attack of immune cells that would otherwise have the task of defending “self ” from “foreign.” Still, maternal cells must be capable of mounting some protective response against bacteria or pathogens that may harm the fetus [1]
We identified two subsets of CD14+ myeloid cells that differ in terms of functional responses to TLR stimulation and cell surface receptors and have a very distinct transcriptional profile
We find that our HLA-DRhigh cells produce more IL-10 and express higher level of EBI3, a subunit of IL-27 and IL-35, two members of the IL-12 family of cytokines
Summary
Pregnancy is a unique situation during which a truly hemi-allogeneic tissue is well protected from the attack of immune cells that would otherwise have the task of defending “self ” from “foreign.” Still, maternal cells must be capable of mounting some protective response against bacteria or pathogens that may harm the fetus [1]. The placenta is heavily infiltrated from immune cells throughout pregnancy [3, 4]. The two most prominent cell types in the placenta are NK cells and macrophages, both of which exert distinct and cooperative functions. They are involved in trophoblast invasion, spiral artery remodeling and angiogenesis, removal of apoptotic cells, and protection of the implant from infections [3, 5]. To understand how tolerance is enforced in human placenta, we evaluated dendritic cell (DC) representation in this tissue, as DCs are key to maintain peripheral tolerance [6]. We found very few DCs in the basal plate (BP) of normal term human placenta. We instead directed our attention to a subset of CD14+ MHC classIIhigh myeloid cells, most likely macrophages, that based on functional studies and unbiased gene array profiling appear to have tolerogenic and regulatory properties
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call