2014
DOI: 10.1159/000358550
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Hierarchical Maturation of Innate Immune Defences in Very Preterm Neonates

Abstract: Background: Preterm neonates are highly vulnerable to infection. Objectives: To investigate the developmental contribution of prematurity, chorioamnionitis and antenatal corticosteroids (ANS) on the maturation of neonatal microbial pathogen recognition responses. Methods: Using standardized protocols, we assayed multiple inflammatory cytokine responses (IL-1β, IL-6, TNF-α and IL-12/23p40) to three prototypic Toll-like receptor (TLR) agonists, i.e. TLR4 (lipopolysaccharide), TLR5 (flagellin) and TLR7/8 (R848), … Show more

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Cited by 31 publications
(32 citation statements)
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“…We confirm profoundly attenuated post-natal responses, consistent with responses measured on cord blood (7,8). The use of single-cell flow cytometry allows confirmation that the functional attenuation in TLR responsiveness is not due to a lack of innate immune cell composition.…”
Section: Discussionsupporting
confidence: 80%
See 1 more Smart Citation
“…We confirm profoundly attenuated post-natal responses, consistent with responses measured on cord blood (7,8). The use of single-cell flow cytometry allows confirmation that the functional attenuation in TLR responsiveness is not due to a lack of innate immune cell composition.…”
Section: Discussionsupporting
confidence: 80%
“…Toll-like receptors (TLRs) play a predominant role as a major family of PRR that act as essential "detectors" in the recognition of microbial pathogens by the innate immune system. We and others have shown that TLR-induced cytokine immune reactivity are profoundly attenuated in cord blood of very preterm neonates and develops asynchronously over the last trimester of gestation (6)(7)(8)(9)(10). These infants also display sustainably high levels of systemic inflammation, indicating a potential immune dysregulation that has also been associated with worsened clinical outcomes (11).…”
mentioning
confidence: 95%
“…Antimicrobial immune recognition and antigen presentation are also significantly impaired at this gestation even in "classical" high CD14-expressing monocytes, because of reduced receptor expression and intracellular signaling [9,10]. In fact, below 20-24 weeks of gestation, our data suggest little activity in extracellular PRR although this gestational age group was not included in studies [11][12][13][14][15]. By comparison, PRR activity in mononuclear cells increases until about 33 weeks of gestation, with the earliest activity detected in endosomal (TLR7, 8 and 9) and intracellular (e.g.…”
Section: Box 2 Relative Importance Of the Innate And Adaptive Immune mentioning
confidence: 74%
“…The significance of this "inside-out" hierarchical development of PRR function during fetal ontogeny is unclear [14]. However, it may important clinical implications.…”
Section: Box 2 Relative Importance Of the Innate And Adaptive Immune mentioning
confidence: 99%
“…In preterm infants, the decreased functionality of TLR4 is associated with a reduced receptor expression on cord blood mononuclear cells, supporting the pivotal role of TLR4 in increased susceptibility to infection (25,26). Of note, microRNAs have emerged as fine modulators of TLRs signaling (27), proving to be a bridge between innate and adaptive immune response.…”
Section: Function Of the Innate Immunitymentioning
confidence: 90%