This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Human newborns are prone to microbial infection and mount poor memory responses to multiple antigens, suggesting functional immunodeficiency at birth. We have previously demonstrated that human neonatal cord blood monocytes show impaired TLR-mediated production of pro-inflammatory/Th1-polarizing cytokines such as TNF-alpha and IL-12 in response to agonists of TLRs 1-7. In marked contrast, TLR8 (and TLR7/8) agonists, including small antiviral imidazoquinoline compounds and single stranded viral RNAs, were uniquely capable of activating inflammatory/Th1-polarizing responses in neonatal blood monocytes and myeloid DCs, suggesting unique efficacy of TLR8 agonists in activating neonatal immune responses. Our current studies are aimed at characterizing the maturation of TLR responses in neonates and infants.
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