The Ability of Fetal Phagocytes to Initiate Adaptive Immunity against Pathogens and Cancers

Fetal or neonatal immunity is considered to bias towards Th2 phenotype. Th2-skewed immunity has a negative effect on recruitment of CD8 cytotoxic lymphocyte precursors into mature effector cells. Fetal or neonatal tolerization is ascribed to the deviation towards non-protective Th2 immunity rather than the inability to mount cytotoxic lymphocyte responses due to immunological immaturity. Following in utero exposure to OVA, immunologically immature murine fetuses couldn’t be tricked into tolerating OVA but rather develop Th2 immunity. Such in utero sensitization was caused by fetal phagocytes that attenuated proteolysis to sequester internalized OVA and differentiated towards dendritic cells for delayed presentation. Our studies revealed the identity of these fetal phagocytes as yolk sac-derived macrophages, which were dendritic cell progenitors to play a decisive role in initiating Th2 immunity regardless of T-cell maturity that has long been a matter of concern. When loaded with allergens, fetal phagocytes were more immunogenic than well-differentiated dendritic cells. Surprisingly, when pulsed with pathogen antigens or oncoprotein, fetal phagocytes exhibited the protective effects against pathogens and cancers, which are usually related to Th1 immunity. This current proposal aims to evaluate whether antigen-loaded fetal phagocytes can elicit Th1 immunity to defend against pathogens or cancers so that we can manipulate these cells for preventive or even therapeutic applications against pathogens or cancers.

Project ID:PC10508-0349
External Project ID:MOST105-2314-B182-053