Genomic Programming of Human Neonatal Dendritic Cells in Congenital Systemic and In Vitro Cytomegalovirus Infection Reveal Plastic and Robust Immune Pathway Biology Responses

摘要: Neonates and especially premature infants are highly susceptible to infection but still can have a remarkable resilience that is poorly understood. The view neonates an incomplete or deficient immune system changing. Human neonatal studies challenging, elucidating host protective responses underlying cognate pathway biology, in the context of viral early life, remains be fully explored. In both resource rich poor settings, human cytomegalovirus (HCMV) most common cause congenital infection. By using unbiased systems analyses transcriptomic resources for HCMV infection, we find systemic response preterm involves focused IFN regulatory associated with dendritic cells. Further analysis transcriptional-programming cells culture revealed dominant IFN-chemokine subnetworks, at later times plasticity pathways implicated cell-cycle control lipid metabolism. Further, identify previously unknown suppressed networks including select group GPCRs. Functional siRNA growth screen targeting 516-GPCRs subsequent validation identified novel GPCR-dependent antiviral (ADORA1) proviral (GPR146, RGS16, PTAFR, SCTR, GPR84, GPR85, NMUR2, FZ10, RDS, CCL17, SORT1) roles. contrast gene family cluster protocadherins significantly differentially induced cells, suggestive possible immunomodulatory Unexpectedly, programming adult upon demonstrated comparable quantitative qualitative showing functionally, cell not overly compromised. However, delay subnetworks comparison adult-derived notable, subtle differences. These findings support set-point mechanism rather than immaturity explaining only susceptibility also summary, our show leads plastic functional robust vivo vitro. adults, minimal number temporal differences may contribute variability resilience, dependent manner.