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Evaluation of the neonatal immune response: basic mechanisms of activation via Toll-like receptors 2 and 4 (TLR-2 and 4) in different antigen presenting cells from healthy term and preterm newborns and with early and late onset sepsis

Grant number: 09/54246-5
Support type:Regular Research Grants
Duration: March 01, 2010 - February 28, 2013
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Patricia Palmeira Daenekas Jorge
Grantee:Patricia Palmeira Daenekas Jorge
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The immaturity of the neonatal immune system has been suggested as the underlying factor for the susceptibility to infections e for the high rate of morbidity and mortality observed in this period. An efficient neonatal T-cell response requires the activation of antigen-presenting cells (APCs), which is triggered upon Toll-like receptors (TLRs) stimulation in response to their respective ligands, leading to the activation of a downstream signaling network and culminating in the translocation of transcription factors to the nucleus, and consequent expression of genes mediating the inflammatory response. Sepsis in the neonatal period is the cause of elevated morbidity and mortality and, the lower is the gestational age and weight at birth, the higher is the incidence of sepsis, as its incidence is related with an immune system even more immature observed in preterm neonates. The aims are to evaluate the activation and response of total mononuclear cells, monocytes and monocyte-derived dendritic cells (MDDCs) from umbilical cord blood of healthy adequate-for-gestational-age term and preterm newborns, as well as from blood of neonates with early and late onset sepsis after ex-vivo TLR-2 and TLR-4 stimulation. Pro- and anti-inflammatory cytokine serum levels and leukocyte populations in cord blood from healthy and septic neonates will be evaluated by flow cytometry. The phagocytic and microbicidal ability of phagocytes will be also determined. Mononuclear cells, monocytes and MDDCs isolates from cord blood and from blood of septic neonates will be stimulated via TLR-2 and 4 with peptidoglycan and LPS respectively and, afterwards, the protein and gene expression levels of pro- and anti-inflammatory cytokines and the expression profiles of the TLR-2 and 4 downstream signaling proteins will be determined. (AU)

Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SILVEIRA-LESSA, ANA LUCIA; QUINELLO, CAMILA; LIMA, LAILA; COSTA REDONDO, ANA CAROLINA; JURFEST RIVERO CECCON, MARIA ESTHER; CARNEIRO-SAMPAIO, MAGDA; PALMEIRA, PATRICIA. TLR expression, phagocytosis and oxidative burst in healthy and septic newborns in response to Gram-negative and Gram-positive rods. HUMAN IMMUNOLOGY, v. 77, n. 10, p. 972-980, OCT 2016. Web of Science Citations: 4.
RENNO, C.; NADAF, M. I. V.; ZAGO, C. A.; CARNEIRO-SAMPAIO, M.; PALMEIRA, P. Healthy Preterm Newborns Show an Increased Frequency of CD4(+)CD25(high)CD127(low)FOXP3(+) Regulatory T Cells with a Naive Phenotype and High Expression of Gut-Homing Receptors. Scandinavian Journal of Immunology, v. 83, n. 6, p. 445-455, JUN 2016. Web of Science Citations: 3.
QUINELLO, C.; SILVEIRA-LESSA, A. L.; CECCON, M. E. J. R.; CIANCIARULLO, M. A.; CARNEIRO-SAMPAIO, M.; PALMEIRA, P. Phenotypic Differences in Leucocyte Populations among Healthy Preterm and Full-Term Newborns. Scandinavian Journal of Immunology, v. 80, n. 1, p. 57-70, JUL 2014. Web of Science Citations: 12.
QUINELLO‚ C.; SILVEIRA-LESSA‚ AL; CIANCIARULLO‚ MA; REDONDO‚ ACC; CECCON‚ M.; CARNEIRO-SAMPAIO‚ M.; PALMEIRA‚ P. P025 Cytokine profile of healthy preterm and term cord blood and peripheral blood of septic newborns. CYTOKINE, v. 59, n. 3, p. 526, 2012.
SILVEIRA-LESSA‚ AL; QUINELLO‚ C.; CIANCIARULLO‚ MA; CECCON‚ M.; CARNEIRO-SAMPAIO‚ M.; PALMEIRA‚ P. P148 TLR-2 and TLR-4 mediated responses in monocytes from preterm and term newborns are distinct from those of adults. CYTOKINE, v. 59, n. 3, p. 567-568, 2012.

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