title: A novel role for interleukin-1 receptor signaling in the developmental regulation of immune responses to endotoxin.
abstract: Neonatal Innate immunity is distinct compared with later ages with some inflammatory cytokines produced in excess of adult levels in response to microbial products such as lipopolysaccharide (LPS). The molecular mechanisms underpinning this specific pattern of neonatal immunity are unknown. In this study, we compared gene expression and cytokine production from LPS stimulated mononuclear cell cultures from 60 individuals at birth and at 12-months. Neonatal mononuclear cell responses were characterized by high levels of IL-1β, IL-10, and IFNγ compared with mononuclear cell responses at 12 months. Microarray analysis of gene expression revealed widespread differences between the neonatal versus infant LPS response. We found expression of a subset of interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) signaling genes was highly expressed in the neonatal period and rapidly down regulated by 12 months. The data suggest that IL-1R1 expression in the neonatal period provides an additional level of Myd88-dependent signaling during this period of heighted susceptibility to infection.
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Martino
authors.forename: Patrick
authors.initials: P
authors.lastname: Holt
authors.forename: Susan
authors.initials: S
authors.lastname: Prescott
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005312:Fetal Blood; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D053573:Receptors, Interleukin-1 Type I / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000276:immunology
chemical_list: D016207:Cytokines; C508590:IL1R1 protein, human; D008070:Lipopolysaccharides; D053573:Receptors, Interleukin-1 Type I; D051193:Toll-Like Receptors