title: Reduced TNF-α response in preterm neonates is associated with impaired nonclassic monocyte function.
abstract: Premature infants are highly susceptible to severe bacterial infections. The impaired infection control related to the functional immaturity of the neonatal innate immune system is an important cause of infection. Different monocyte subpopulations have been described and functionally characterized. However, data from preterm infants are scarce. We analyzed constitutive monocyte TLR2, TLR4, CD163, and HLA-DR expression in preterm cord blood. We further investigated activation of the signaling proteins ERK1/2 and NF-κB in monocyte subpopulations after ex vivo stimulation with the bacterial TLR agonists LPS and lipoteichoic acid. The functional outcome of the stimulation was determined by the intracellular production of TNF. Furthermore, the phagocytic activity was measured via flow cytometry. TLR4 and HLA-DR showed a gestational age-dependent increase. However, activation of ERK1/2 and NF-κB was impaired in neonatal monocyte subpopulations after stimulation with TLR agonists. Accordingly, intracellular TNF was diminished in preterm monocytes, especially in nonclassic monocytes. Premature monocytes showed high phagocytic activity, with significantly lower acidification of the phagosome. The reduced functional response of nonclassic monocytes of preterm neonates appears to be part of the diminished early immune response to bacterial cell wall components and is likely to contribute to their susceptibility to bacterial infection.
authors.affiliation: Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria lukas.wisgrill@meduniwien.ac.at.
authors.forename: Lukas
authors.initials: L
authors.lastname: Wisgrill
authors.affiliation: Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Alina
authors.initials: A
authors.lastname: Groschopf
authors.affiliation: Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Herndl
authors.affiliation: Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Kambis
authors.initials: K
authors.lastname: Sadeghi
authors.affiliation: Department of Surgery and Core Facility Flow Cytometry, Medical University of Vienna, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Spittler
authors.affiliation: Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Berger
authors.affiliation: Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Förster-Waldl
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005312:Fetal Blood / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005865:Gestational Age; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D055815:Young Adult; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006684:HLA-DR Antigens; D011956:Receptors, Cell Surface; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha
keywords: Toll-like receptor; monocytes subsets; neonatal immunity; very-low-birth weight infants