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TLR3 impairment in human newborns

Lucija Slavica1, Inger Nordström, Merja Nurkkala Karlsson

  • 11.University of Gothenburg, Guldhedsgatan 10A, Gothenburg, Sweden. lucija.slavica@rheuma.gu.se.

Journal of Leukocyte Biology
|August 1, 2013
PubMed

Insights

Newborns exhibit heightened susceptibility to viral infections due to underdeveloped innate immunity. Specifically, cord blood NK cells show deficient TLR3 expression, impairing their response to viral stimuli like HSV and contributing to neonatal infection vulnerability.

Area of Science:

  • Immunology
  • Neonatal Immunology
  • Infectious Disease

Background:

  • Newborns are vulnerable to viral infections.
  • Innate immune responses, including virus-sensing receptors, are crucial for defense.
  • Toll-like receptor 3 (TLR3) plays a role in antiviral immunity.

Purpose of the Study:

  • To investigate the expression and function of innate virus-sensing receptors, particularly TLR3, in newborn immune cells.
  • To understand the role of TLR3 in Natural Killer (NK) cell responses to viral stimulation in neonates.
  • To elucidate the mechanisms underlying neonatal susceptibility to viral infections.

Main Methods:

  • Analysis of mRNA and protein expression of TLR3, TLR7, TLR8, TLR9, RIG-I, MDA5, PKR, and IFI16 in cord blood mononuclear cells (CBMCs) and peripheral blood mononuclear cells (PBMCs).
  • Functional assays assessing IFN-γ production and cytotoxic activity of cord blood NK cells upon stimulation with poly(I:C) and herpes simplex virus (HSV).
  • Comparison of TLR3 expression in NK cells from cord blood, adult peripheral blood, and decidual samples.

Main Results:

  • CBMCs expressed mRNA for most innate receptors, but lacked TLR3 mRNA.
  • TLR3 mRNA was found in adult PBMCs, particularly in CD56(dim) NK cells, but was low in cord blood NK cells and absent as protein.
  • Cord blood NK cells showed impaired IFN-γ production and cytotoxicity in response to poly(I:C) and HSV, unlike adult NK cells.

Conclusions:

  • Cord blood NK cells exhibit deficient TLR3 expression and impaired responses to TLR3 ligands and HSV.
  • This deficiency in TLR3-mediated immunity may explain the increased susceptibility of newborns to viral infections, such as neonatal HSV infections.
  • TLR3 expression is not influenced by sex hormones but is low in decidual NK cells due to their CD56(bright) phenotype.

Keywords:
cord NK cellsdecidual NK cellspoly(I:C)

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