title: Preterm infants have deficient monocyte and lymphocyte cytokine responses to group B streptococcus.
abstract: Group B streptococcus (GBS) is an important cause of early- and late-onset sepsis in the newborn. Preterm infants have markedly increased susceptibility and worse outcomes, but their immunological responses to GBS are poorly defined. We compared mononuclear cell and whole-blood cytokine responses to heat-killed GBS (HKGBS) of preterm infants (gestational age [GA], 26 to 33 weeks), term infants, and healthy adults. We investigated the kinetics and cell source of induced cytokines and quantified HKGBS phagocytosis. HKGBS-induced tumor necrosis factor (TNF) and interleukin 6 (IL-6) secretion was significantly impaired in preterm infants compared to that in term infants and adults. These cytokines were predominantly monocytic in origin, and production was intrinsically linked to HKGBS phagocytosis. Very preterm infants (GA, <30 weeks) had fewer cytokine-producing monocytes, but nonopsonic phagocytosis ability was comparable to that for term infants and adults. Exogenous complement supplementation increased phagocytosis in all groups, as well as the proportion of preterm monocytes producing IL-6, but for very preterm infants, responses were still deficient. Similar defective preterm monocyte responses were observed in fresh whole cord blood stimulated with live GBS. Lymphocyte-associated cytokines were significantly deficient for both preterm and term infants compared to levels for adults. These findings indicate that a subset of preterm monocytes do not respond to GBS, a defect compounded by generalized weaker lymphocyte responses in newborns. Together these deficient responses may increase the susceptibility of preterm infants to GBS infection.
authors.affiliation: School of Veterinary & Biomedical Sciences, Murdoch University, Murdoch, Western Australia. a.currie@murdoch.edu.au
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Currie
authors.forename: Samantha
authors.initials: S
authors.lastname: Curtis
authors.forename: Tobias
authors.initials: T
authors.lastname: Strunk
authors.forename: Karen
authors.initials: K
authors.lastname: Riley
authors.forename: Khemanganee
authors.initials: K
authors.lastname: Liyanage
authors.forename: Susan
authors.initials: S
authors.lastname: Prescott
authors.forename: Dorota
authors.initials: D
authors.lastname: Doherty
authors.forename: Karen
authors.initials: K
authors.lastname: Simmer
authors.forename: Peter
authors.initials: P
authors.lastname: Richmond
authors.forename: David
authors.initials: D
authors.lastname: Burgner
mesh_terms: D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D018805:Sepsis / Q000276:immunology / Q000382:microbiology; D013290:Streptococcal Infections / Q000276:immunology; D013292:Streptococcus agalactiae / Q000276:immunology*
chemical_list: D016207:Cytokines