INTRODUCTION: Staphylococcus epidermidis (SE) rarely causes infection in term infants but is a leading cause of late-onset sepsis in preterm infants. We hypothesized that the innate immune responses to SE in preterm infants are impaired in a gestational age (GA)-dependent manner. METHODS: Cord and peripheral blood mononuclear cells (MNCs) were stimulated with SE bacteria, and a range of innate immune responses were assessed, including phagocytosis, intracellular killing, Toll-like receptor (TLR) pathway transcriptional activation, cytokine production, TLR2 and TLR4 expression, and cell signaling. RESULTS: Phagocytosis and intracellular killing of SE bacteria were similar in neonatal and adult monocytes. Cytokine gene expression and protein synthesis increased in a GA-dependent manner, which was confirmed at the single-cell level. These GA-related effects were not associated with differences in expression of TLR2 or TLR4, nor with downstream activation of nuclear factor-κB or mitogen-activated protein kinase pathways. DISCUSSION: The expression of TLRs, phagocytic capacity, and intracellular killing by monocytes develops early in fetal development, whereas the ability to mount a bacteria-induced cytokine response requires further maturation. The functional immaturity of monocyte activation pathways in the preterm infant may underpin their particular susceptibility to sepsis with commensal bacteria.
INTRODUCTION:Staphylococcus epidermidis (SE) rarely causes infection in term infants but is a leading cause of late-onset sepsis in preterm infants. We hypothesized that the innate immune responses to SE in preterm infants are impaired in a gestational age (GA)-dependent manner. METHODS: Cord and peripheral blood mononuclear cells (MNCs) were stimulated with SE bacteria, and a range of innate immune responses were assessed, including phagocytosis, intracellular killing, Toll-like receptor (TLR) pathway transcriptional activation, cytokine production, TLR2 and TLR4 expression, and cell signaling. RESULTS: Phagocytosis and intracellular killing of SE bacteria were similar in neonatal and adult monocytes. Cytokine gene expression and protein synthesis increased in a GA-dependent manner, which was confirmed at the single-cell level. These GA-related effects were not associated with differences in expression of TLR2 or TLR4, nor with downstream activation of nuclear factor-κB or mitogen-activated protein kinase pathways. DISCUSSION: The expression of TLRs, phagocytic capacity, and intracellular killing by monocytes develops early in fetal development, whereas the ability to mount a bacteria-induced cytokine response requires further maturation. The functional immaturity of monocyte activation pathways in the preterm infant may underpin their particular susceptibility to sepsis with commensal bacteria.
Authors: Elizabeth A Marchant; Bernard Kan; Ashish A Sharma; Alice van Zanten; Tobias R Kollmann; Rollin Brant; Pascal M Lavoie Journal: Pediatr Res Date: 2015-07-17 Impact factor: 3.756
Authors: Ashish A Sharma; Roger Jen; Bernard Kan; Abhinav Sharma; Elizabeth Marchant; Anthony Tang; Izabelle Gadawski; Christof Senger; Amanda Skoll; Stuart E Turvey; Laura M Sly; Hélène C F Côté; Pascal M Lavoie Journal: Eur J Immunol Date: 2014-11-17 Impact factor: 5.532
Authors: Emma de Jong; David G Hancock; Julie Hibbert; Christine Wells; Peter Richmond; Karen Simmer; David Burgner; Tobias Strunk; Andrew J Currie Journal: J Mol Med (Berl) Date: 2017-11-13 Impact factor: 4.599