Impaired innate immune responses in human neonates

Abstract

Human newborns are at greater risk of infection than children and adults because of the immaturity of their immune system. Mononuclear phagocytes from the cord generate blunted responses to an array of toll-like receptor (TLR) ligands and to physiologic stimuli of the inflammatory response. Neonatal deficiency of innate cellular immunity includes a decreased production of interferons, interleukin (IL)-12/IL-23, and IL-18, and other proinflammatory cytokines, an impaired type-1 response of macrophages to IFN-γ, the most potent macrophage-activating agent in vivo, and to lipopolysaccharide, the primary constituent of the outer membrane of Gram-negative bacteria. This review will describe recent advances in understanding innate cellular immunity in human neonates. As we learn more about neonatal innate immunity, new therapeutic avenues may come into sight. Drug development efforts could be directed toward augmenting innate cellular immune responses to prevent and treat neonatal infections more accurately.