Responsiveness of human monocytes to the commensal bacterium Staphylococcus epidermidis develops late in gestation
Strunk, T., Prosser, A., Levy, O., Philbin, V., Simmer, K., Doherty, D., Charles, A., Richmond, P., Burgner, D. and Currie, A. (2012) Responsiveness of human monocytes to the commensal bacterium Staphylococcus epidermidis develops late in gestation. Pediatric Research, 72 (1). pp. 10-18.
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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.
|Publication Type:||Journal Article|
|Murdoch Affiliation:||School of Veterinary and Biomedical Sciences|
|Publisher:||Lippincott Williams & Wilkins Ltd|
|Copyright:||© 2012 International Pediatric Research Foundation, Inc|
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