Neonatal Innate TLR-Mediated Responses Are Distinct from Those of Adults

TLDR

Neonates are highly susceptible to infection because their innate and adaptive immune systems differ from adults, yet the precise nature of these differences remains incompletely defined. The study aims to define differences in TLR‑mediated responses between human neonates and adults. The authors performed a comprehensive analysis of TLR ligation responses in neonatal and adult innate immune cells. Neonatal innate immune cells produce lower IL‑12p70, IFN‑α, and IFN‑γ, and moderately less TNF‑α, but comparable or higher IL‑1β, IL‑6, IL‑23, and IL‑10, are less polyfunctional, and overall favor Th17/Th2 responses while showing reduced Th1 capacity compared to adults.

Abstract

Abstract The human neonate and infant are unduly susceptible to infection with a wide variety of microbes. This susceptibility is thought to reflect differences from adults in innate and adaptive immunity, but the nature of these differences is incompletely characterized. The innate immune response directs the subsequent adaptive immune response after integrating information from TLRs and other environmental sensors. We set out to provide a comprehensive analysis defining differences in response to TLR ligation between human neonates and adults. In response to most TLR ligands, neonatal innate immune cells, including monocytes and conventional and plasmacytoid dendritic cells produced less IL-12p70 and IFN-α (and consequently induced less IFN-γ), moderately less TNF-α, but as much or even more IL-1β, IL-6, IL-23, and IL-10 than adult cells. At the single-cell level, neonatal innate cells generally were less capable of producing multiple cytokines simultaneously, i.e., were less polyfunctional. Overall, our data suggest a robust if not enhanced capacity of the neonate vs the adult white-blood cell TLR-mediated response to support Th17- and Th2-type immunity, which promotes defense against extracellular pathogens, but a reduced capacity to support Th1-type responses, which promote defense against intracellular pathogens.