BACKGROUND: The human neonate's increased susceptibility to bacterial infections is not completely understood. Toll-like receptors (TLRs) have been recognized as pattern-recognition receptors critical to the innate immune response. TLR function in neonates, however, remains incompletely defined. OBJECTIVE: To examine regulatory and proinflammatory cytokine responses to TLR-1-6 stimulation of cord blood compared to adult blood. METHODS: We stimulated cord blood with ligands for each of TLRs 1-6 and compared these responses to adult controls. The following TLR ligands were utilized: Pam3CSK4 (TLR-1 and 2), zymosan (TLR-2 and 6), poly I:C (TLR-3), LPS (TLR-4), and flagellin (TLR-5). Cytokine production was measured with an assay developed in-house utilizing multi-analyte technology. RESULTS: TLR-1-6 stimulation produced higher concentrations of proinflammatory cytokines (IL-1beta, IL-6, and IL-8) in cord blood compared to adult blood, with the exception of TLR-4-stimulated TNF-alpha production, which was significantly lower in cord blood (319 pg/ml) compared to adult blood (645 pg/ml; p = 0.027). In contrast, TLR-1-6 stimulation resulted in decreased concentrations of Th1 and Th2 cytokines in cord blood compared to adult blood, with significantly diminished production of IL-12 (TLRs 1/2, 2/6, 3 and 4), IL-13 (TLR-1-6), and IL-10 (TLR-4). CONCLUSION: Cord blood production of regulatory Th1 and Th2 cytokines following TLR stimulation is decreased compared to that of adult blood. In contrast, TLR-stimulated proinflammatory cytokine production was markedly higher in neonates than in adults, with the exception of TLR-4-induced TNF-alpha production. The human neonate's increased susceptibility to bacterial infections may be related to abnormal TLR responsiveness, with enhanced proinflammatory and decreased regulatory cytokine production. Copyright 2009 S. Karger AG, Basel.
BACKGROUND: The human neonate's increased susceptibility to bacterial infections is not completely understood. Toll-like receptors (TLRs) have been recognized as pattern-recognition receptors critical to the innate immune response. TLR function in neonates, however, remains incompletely defined. OBJECTIVE: To examine regulatory and proinflammatory cytokine responses to TLR-1-6 stimulation of cord blood compared to adult blood. METHODS: We stimulated cord blood with ligands for each of TLRs 1-6 and compared these responses to adult controls. The following TLR ligands were utilized: Pam3CSK4 (TLR-1 and 2), zymosan (TLR-2 and 6), poly I:C (TLR-3), LPS (TLR-4), and flagellin (TLR-5). Cytokine production was measured with an assay developed in-house utilizing multi-analyte technology. RESULTS:TLR-1-6 stimulation produced higher concentrations of proinflammatory cytokines (IL-1beta, IL-6, and IL-8) in cord blood compared to adult blood, with the exception of TLR-4-stimulated TNF-alpha production, which was significantly lower in cord blood (319 pg/ml) compared to adult blood (645 pg/ml; p = 0.027). In contrast, TLR-1-6 stimulation resulted in decreased concentrations of Th1 and Th2 cytokines in cord blood compared to adult blood, with significantly diminished production of IL-12 (TLRs 1/2, 2/6, 3 and 4), IL-13 (TLR-1-6), and IL-10 (TLR-4). CONCLUSION: Cord blood production of regulatory Th1 and Th2 cytokines following TLR stimulation is decreased compared to that of adult blood. In contrast, TLR-stimulated proinflammatory cytokine production was markedly higher in neonates than in adults, with the exception of TLR-4-induced TNF-alpha production. The human neonate's increased susceptibility to bacterial infections may be related to abnormal TLR responsiveness, with enhanced proinflammatory and decreased regulatory cytokine production. Copyright 2009 S. Karger AG, Basel.
Authors: Darren Blimkie; Edgardo S Fortuno; Howard Yan; Patricia Cho; Kevin Ho; Stuart E Turvey; Arnaud Marchant; Stanislas Goriely; Tobias R Kollmann Journal: J Immunol Methods Date: 2011-01-28 Impact factor: 2.303
Authors: Jelske W van der Burg; Sarbattama Sen; Virginia R Chomitz; Jaap C Seidell; Alan Leviton; Olaf Dammann Journal: Pediatr Res Date: 2015-09-16 Impact factor: 3.756
Authors: Elaine Cristina Cardoso; Nátalli Zanete Pereira; Gabrielle Eimi Mitsunari; Luanda Mara da Silva Oliveira; Rosa Maria S A Ruocco; Rossana Pulcineli Vieira Francisco; Marcelo Zugaib; Alberto José da Silva Duarte; Maria Notomi Sato Journal: PLoS One Date: 2013-06-27 Impact factor: 3.240