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

Division of Infectious and Immunological Diseases, Department of Pediatrics, University of British Columbia, CFRI, 950 West 28th Avenue, Vancouver, BC, V5Z4H4, Canada.
The Journal of Immunology (Impact Factor: 4.92). 11/2009; 183(11):7150-60. DOI: 10.4049/jimmunol.0901481
Source: PubMed


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-alpha (and consequently induced less IFN-gamma), moderately less TNF-alpha, but as much or even more IL-1beta, 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.

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Available from: Pascal M Lavoie, Dec 11, 2014
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    • "Isolated neonatal T cells have a lower proliferative capacity and secrete lower amounts of IFN-gamma after polyclonal stimulation in vitro. In vivo, the ability of neonatal T cells to mount effective responses is likely influenced by the lower expression of B7 family molecules on antigen-presenting cells (APCs) [39] and the defective cytokine production by these cells [40]. T cell responses induced by several routine vaccines are less polyfunctional, less proliferative and produce lower IFN-gamma in infants compared to adults [41]–[47]. "
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    PLoS ONE 09/2014; 9(9):e107816. DOI:10.1371/journal.pone.0107816 · 3.23 Impact Factor
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    • "Innate immune responses in early life are also distinct from those in adulthood. In particular, triggering of most toll-like receptors (TLR) ligands in neonatal leukocyte populations yields less IL-12, type 1 IFN, and TNFα, but enhanced levels of IL-1, IL-6, IL-23, and IL-10 relative to corresponding adult cells; overall, the neonatal innate response profile supports robust Th-2 and Th-17 immunity while Th-1 immunity is attenuated (74). "
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    Frontiers in Immunology 09/2014; 5:447. DOI:10.3389/fimmu.2014.00447
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    • "Age dependent differences in human immunity are implied by the clinical observation of altered disease susceptibility and substantiated by differences in immune cell activities. Newborns are more susceptible to several diseases when compared to adults; this appears to be at least partially due to a lack of acquired immune memory and differential regulation of innate immune responses (7, 8). This altered immunological priming is not maladaptive, rather, the fetus and neonate are challenged with balancing defense against infection, minimizing potentially harmful inflammation, and mitigating colonization by microbes as it develops and transitions from the relatively protected womb to the external world (9). "
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