Characterization of innate immunity in mouse embryonic stem cells, trophoblast stem cells, and their differentiated cells
Mona Fendereski and Yan-Lin Guo
The University of Southern Mississippi, Hattiesburg, MS
Innate immunity is an evolutionarily conserved defense mechanism presumably developed in all cell types. Innate immune system can be activated by various immune stimuli, leading to the expression of interferons (IFNs) and inflammatory cytokines that participate in different aspects of immune and inflammatory responses. Surprisingly, our recent studies demonstrated that mouse embryonic stem cells (ESCs) are deficient in innate immune responses. In particular, they are deficient in expressing IFNs and lack responses to bacterial endotoxin and inflammatory cytokines. This finding challenges the concept of innate immunity as an inborn defense mechanism. ESCs are derived from inner cell mass of the blastocyst, the early embryo which is surrounded by trophectoderm that gives raise to placenta. In this study, we extended our investigation to determine the immunoproperties of mouse trophoblast stem cells (TSCs), the progenitors of placental cells. Through in vitro differentiation, we are able to differentiate TSCs into trophoblast giant cells (TGCs), the primitive placental cells. We tested the responses of TSCs and TGCs to LPS and TNFα, two inflammatory agents that strongly induce inflammatory responses in embryonic fibroblasts. Both TSCs and TGCs failed to respond to LPS and TNFα as assessed by inflammatory gene induction and the lack of NFκB activation, the transcription factor that mediates the effects of LPS and TNFα. Surprisingly, TSCs can express IFNβ, suggesting that they have a functional IFN antiviral mechanism. Our data suggest that the immunologic properties of TSCs and ESCs are developmentally different, therefore may have important implications during early embryogenesis.