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Statements

Subject Item
n2:RIV%2F00216208%3A11150%2F13%3A10196506%21RIV14-MSM-11150___
rdf:type
skos:Concept n15:Vysledek
rdfs:seeAlso
http://dx.doi.org/10.1189/jlb.1212617
dcterms:description
Newborns are highly susceptible to viral infections. We hypothesized that this susceptibility could be due to a dysregulated expression of innate virus-sensing receptors, i.e., TLR3, TLR7, TLR8, and TLR9 and the cytosolic receptors retinoic acid-inducible gene I, melanoma differentiation-associated protein 5, protein kinase R, and IFN-gamma-inducible protein 16. Cord blood mononuclear cells (CBMCs) expressed mRNA for all these receptors except for TLR3. In peripheral blood mononuclear cells (PBMCs), TLR3 mRNA was preferentially expressed in cytotoxic cells, particularly CD56(dim) NK cells. Cord NK cells in contrast showed low TLR3 mRNA expression and lacked TLR3 protein expression. Cord NK cells did not produce IFN-gamma in response to polyinosinic-polycytidylic acid [poly(I:C)], whereas strong IFN-gamma production was observed in poly(I:C)-stimulated adult NK cells. Cord NK cells had poor cytotoxic function that was only marginally enhanced by exposure to the TLR3 ligand poly(I:C). Opposite to NK cells from adults, their cytotoxicity was not improved by herpes simplex virus (HSV) exposure and they were unable to kill HSV-infected cells. There were no differences in the TLR3 mRNA levels among men, women, and pregnant women, implying that TLR3 is not under sex hormone control. However, decidual NK cells expressed low levels of TLR3 mRNA, which was attributed to their CD56(bright) phenotype. Our data show that cord blood NK cells have deficient TLR3 expression associated with an inability to respond to poly(I:C) and HSV activation and to kill HSV-infected cells. This might explain why newborns are particularly sensitive to neonatal HSV infections. Newborns are highly susceptible to viral infections. We hypothesized that this susceptibility could be due to a dysregulated expression of innate virus-sensing receptors, i.e., TLR3, TLR7, TLR8, and TLR9 and the cytosolic receptors retinoic acid-inducible gene I, melanoma differentiation-associated protein 5, protein kinase R, and IFN-gamma-inducible protein 16. Cord blood mononuclear cells (CBMCs) expressed mRNA for all these receptors except for TLR3. In peripheral blood mononuclear cells (PBMCs), TLR3 mRNA was preferentially expressed in cytotoxic cells, particularly CD56(dim) NK cells. Cord NK cells in contrast showed low TLR3 mRNA expression and lacked TLR3 protein expression. Cord NK cells did not produce IFN-gamma in response to polyinosinic-polycytidylic acid [poly(I:C)], whereas strong IFN-gamma production was observed in poly(I:C)-stimulated adult NK cells. Cord NK cells had poor cytotoxic function that was only marginally enhanced by exposure to the TLR3 ligand poly(I:C). Opposite to NK cells from adults, their cytotoxicity was not improved by herpes simplex virus (HSV) exposure and they were unable to kill HSV-infected cells. There were no differences in the TLR3 mRNA levels among men, women, and pregnant women, implying that TLR3 is not under sex hormone control. However, decidual NK cells expressed low levels of TLR3 mRNA, which was attributed to their CD56(bright) phenotype. Our data show that cord blood NK cells have deficient TLR3 expression associated with an inability to respond to poly(I:C) and HSV activation and to kill HSV-infected cells. This might explain why newborns are particularly sensitive to neonatal HSV infections.
dcterms:title
TLR3 impairment in human newborns TLR3 impairment in human newborns
skos:prefLabel
TLR3 impairment in human newborns TLR3 impairment in human newborns
skos:notation
RIV/00216208:11150/13:10196506!RIV14-MSM-11150___
n15:predkladatel
n16:orjk%3A11150
n3:aktivita
n4:N
n3:aktivity
N
n3:cisloPeriodika
5
n3:dodaniDat
n13:2014
n3:domaciTvurceVysledku
n5:1807676
n3:druhVysledku
n9:J
n3:duvernostUdaju
n12:S
n3:entitaPredkladatele
n17:predkladatel
n3:idSjednocenehoVysledku
111179
n3:idVysledku
RIV/00216208:11150/13:10196506
n3:jazykVysledku
n19:eng
n3:klicovaSlova
decidual NK cells; poly(I:C); cord NK cells
n3:klicoveSlovo
n7:cord%20NK%20cells n7:poly%28I%3AC%29 n7:decidual%20NK%20cells
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[EBA200F4A1CE]
n3:nazevZdroje
Journal of Leukocyte Biology
n3:obor
n6:FK
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
7
n3:rokUplatneniVysledku
n13:2013
n3:svazekPeriodika
94
n3:tvurceVysledku
Valadi, Hadi Karlsson, Merja Nurkkala Slavica, Lucija Jacobsson, Bo Eriksson, Kristina Kacerovský, Marian Nordström, Inger
n3:wos
000330537700017
s:issn
0741-5400
s:numberOfPages
9
n20:doi
10.1189/jlb.1212617
n14:organizacniJednotka
11150