title: Neonatal innate TLR-mediated responses are distinct from those of adults.
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-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.
authors.affiliation: Division of Infectious and Immunological Diseases, Department of Pediatrics, University of British Columbia, CFRI, 950 West 28th Avenue, Vancouver, BC, V5Z4H4, Canada. tkollm@mac.com
authors.forename: Tobias R
authors.initials: TR
authors.lastname: Kollmann
authors.forename: Juliet
authors.initials: J
authors.lastname: Crabtree
authors.forename: Annie
authors.initials: A
authors.lastname: Rein-Weston
authors.forename: Darren
authors.initials: D
authors.lastname: Blimkie
authors.forename: Francis
authors.initials: F
authors.lastname: Thommai
authors.forename: Xiu Yu
authors.initials: XY
authors.lastname: Wang
authors.forename: Pascal M
authors.initials: PM
authors.lastname: Lavoie
authors.forename: Jeff
authors.initials: J
authors.lastname: Furlong
authors.forename: Edgardo S
authors.initials: ES
authors.lastname: Fortuno
authors.forename: Adeline M
authors.initials: AM
authors.lastname: Hajjar
authors.forename: Natalie R
authors.initials: NR
authors.lastname: Hawkins
authors.forename: Steven G
authors.initials: SG
authors.lastname: Self
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Wilson
mesh_terms: D000328:Adult; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007223:Infant; D007231:Infant, Newborn / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors