Reduced TNF-α response in preterm neonates is associated with impaired nonclassic monocyte function.
J Leukoc Biol
; 100(3): 607-12, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-26965638
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Recém-Nascido Prematuro
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Monócitos
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Transdução de Sinais
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Fator de Necrose Tumoral alfa
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Sangue Fetal
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Female
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Humans
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Infant
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Male
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Newborn
Idioma:
En
Revista:
J Leukoc Biol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Áustria