dc.contributor.author | Belderbos, Mirjam E. | |
dc.contributor.author | Levy, Ofer | |
dc.contributor.author | Stalpers, Femke | |
dc.contributor.author | Kimpen, Jan L. | |
dc.contributor.author | Meyaard, Linde | |
dc.contributor.author | Bont, Louis | |
dc.date.accessioned | 2012-05-14T04:01:36Z | |
dc.date.issued | 2012 | |
dc.identifier.citation | Belderbos, Mirjam E., Ofer Levy, Femke Stalpers, Jan L. Kimpen, Linde Meyaard, and Louis Bont. 2012. Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors. PLoS ONE 7(3): e33419. | en_US |
dc.identifier.issn | 1932-6203 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:8735555 | |
dc.description.abstract | Human neonates are highly susceptible to infection, which may be due in part to impaired innate immune function. Neonatal Toll-like receptor (TLR) responses are biased against the generation of pro-inflammatory/Th1-polarizing cytokines, yet the underlying mechanisms are incompletely defined. Here, we demonstrate that neonatal plasma polarizes TLR4-mediated cytokine production. When exposed to cord blood plasma, mononuclear cells (MCs) produced significantly lower TLR4-mediated IL-12p70 and higher IL-10 compared to MC exposed to adult plasma. Suppression by neonatal plasma of TLR4-mediated IL-12p70 production, but not induction of TLR4-mediated IL-10 production, was maintained up to the age of 1 month. Cord blood plasma conferred a similar pattern of MC cytokine responses to TLR3 and TLR8 agonists, demonstrating activity towards both MyD88-dependent and MyD88-independent agonists. The factor causing increased TLR4-mediated IL-10 production by cord blood plasma was heat-labile, lost after protein depletion and independent of lipoprotein binding protein (LBP) or soluble CD14 (sCD14). The factor causing inhibition of TLR4-mediated IL-12p70 production by cord blood plasma was resistant to heat inactivation or protein depletion and was independent of IL-10, vitamin D and prostaglandin E2. In conclusion, human neonatal plasma contains at least two distinct factors that suppress TLR4-mediated IL-12p70 production or induce IL-10 or production. Further identification of these factors will provide insight into the ontogeny of innate immune development and might identify novel targets for the prevention and treatment of neonatal infection. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | doi:10.1371/journal.pone.0033419 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307729/pdf/ | en_US |
dash.license | LAA | |
dc.subject | medicine | en_US |
dc.subject | clinical immunology | en_US |
dc.subject | pediatrics | en_US |
dc.title | Neonatal Plasma Polarizes TLR4-Mediated Cytokine Responses towards Low IL-12p70 and High IL-10 Production via Distinct Factors | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | PLoS ONE | en_US |
dash.depositing.author | Levy, Ofer | |
dc.date.available | 2012-05-14T04:01:36Z | |
dc.identifier.doi | 10.1371/journal.pone.0033419 | * |
dash.contributor.affiliated | Levy, Ofer | |