Hierarchical maturation of innate immune defences in very preterm neonates

Ashish Arunkumar Sharma, Roger Jen, Rollin Brant, Mihoko Ladd, Qing Huang, Amanda Skoll, Christof Senger, Stuart E. Turvey, Nico Marr, Pascal M. Lavoie

Research output: Contribution to journalArticle

17 Citations (Scopus)

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), and to the non-TLR retinoic acid-inducible gene I (RIG-I)-like receptor agonist, in cord blood mononuclear cells from neonates born before 33 weeks of gestation and at term. Results: TLR responses develop asynchronously in preterm neonates, whereby responses to TLR7/8 were more mature and were followed by the development of TLR4 responses, which were also heterogeneous. Responses to TLR5 were weakest and most immature. Maturity in TLR responses was not influenced by sex. Overall, we detected no significant contribution of ANS and chorioamnionitis to the developmental attenuation of either TLR or RIG-I responses. Conclusions: The maturation of anti-microbial responses in neonates born early in gestation follows an asynchronous developmental hierarchy independently of an exposure to chorioamnionitis and ANS. Our data provide an immunological basis for the predominance of specific microbial infections in this age group.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalNeonatology
Volume106
Issue number1
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Toll-Like Receptors
Chorioamnionitis
Newborn Infant
Adrenal Cortex Hormones
resiquimod
Flagellin
Pregnancy
Retinoic Acid Receptors
Interleukin-12
Infection
Tretinoin
Fetal Blood
Interleukin-1
Genes
Lipopolysaccharides
Interleukin-6
Blood Cells
Age Groups
Cytokines

Keywords

  • Antenatal corticosteroids
  • Chorioamnionitis
  • Infection
  • Neonate
  • Toll-like receptor

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health
  • Medicine(all)

Cite this

Sharma, A. A., Jen, R., Brant, R., Ladd, M., Huang, Q., Skoll, A., ... Lavoie, P. M. (2014). Hierarchical maturation of innate immune defences in very preterm neonates. Neonatology, 106(1), 1-9. https://doi.org/10.1159/000358550

Hierarchical maturation of innate immune defences in very preterm neonates. / Sharma, Ashish Arunkumar; Jen, Roger; Brant, Rollin; Ladd, Mihoko; Huang, Qing; Skoll, Amanda; Senger, Christof; Turvey, Stuart E.; Marr, Nico; Lavoie, Pascal M.

In: Neonatology, Vol. 106, No. 1, 2014, p. 1-9.

Research output: Contribution to journalArticle

Sharma, AA, Jen, R, Brant, R, Ladd, M, Huang, Q, Skoll, A, Senger, C, Turvey, SE, Marr, N & Lavoie, PM 2014, 'Hierarchical maturation of innate immune defences in very preterm neonates', Neonatology, vol. 106, no. 1, pp. 1-9. https://doi.org/10.1159/000358550
Sharma AA, Jen R, Brant R, Ladd M, Huang Q, Skoll A et al. Hierarchical maturation of innate immune defences in very preterm neonates. Neonatology. 2014;106(1):1-9. https://doi.org/10.1159/000358550
Sharma, Ashish Arunkumar ; Jen, Roger ; Brant, Rollin ; Ladd, Mihoko ; Huang, Qing ; Skoll, Amanda ; Senger, Christof ; Turvey, Stuart E. ; Marr, Nico ; Lavoie, Pascal M. / Hierarchical maturation of innate immune defences in very preterm neonates. In: Neonatology. 2014 ; Vol. 106, No. 1. pp. 1-9.
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