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. 2010 Jul;17(7):1079-85.
doi: 10.1128/CVI.00074-10. Epub 2010 May 12.

Dendritic cells in uninfected infants born to hepatitis B virus-positive mothers

Lemonica J Koumbi  1 , Nikolaos G Papadopoulos, Vassiliki Anastassiadou, Maria Machaira, Dimitris A Kafetzis, Vassiliki Papaevangelou
Affiliations

Dendritic cells in uninfected infants born to hepatitis B virus-positive mothers

Lemonica J Koumbi et al. Clin Vaccine Immunol. 2010 Jul.

Abstract

Plasmacytoid dendritic cells (pDCs) play a central role in antiviral immunity, detecting viruses via Toll-like receptors (TLR) and producing in response vast amounts of type I interferons (IFNs). Hepatitis B virus (HBV) causes chronic infection after vertical transmission. This study investigated whether an HBV-infected maternal environment might influence DC numbers and pDC function in uninfected infants. Blood was collected from inactive HBsAg carrier and control mothers and their infants at birth and 1 and 6 months of age. HBV DNA was measured in maternal and neonatal perinatal sera using real-time PCR. The circulating frequencies of myeloid DCs (mDCs) and pDCs were determined in the babies by flow cytometry. Peripheral blood mononuclear cells (PBMCs) and cord blood pDCs were stimulated with resiquimod, and alpha interferon (IFN-alpha) production and the pDC phenotype were assessed. The effect of the common-cold virus, rhinovirus (RV), on resiquimod stimulation was also determined. HBV DNA was detected in 62.3% of the mothers and 41% of their infants. DC numbers and pDC functions were similar between subjects and controls and were not correlated with maternal or neonatal viremia. RV infection did not induce pDC maturation until the age of 6 months, and it reduced TLR7-dependent resiquimod-induced IFN-alpha production similarly in both groups. Although the DC system is immature at birth, DCs of uninfected neonates of HBV-positive mothers are competent to initiate and maintain T-cell responses. RV is a weak inducer of IFN-alpha production until the age of 6 months and inhibits IFN-alpha responses triggered by the TLR7 pathway.

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Figures

FIG. 1.
FIG. 1.
Representative phenotypic analysis of mDC and pDC subsets by flow cytometry. (a) PBMCs were gated according to their forward (FSC) and side (SSC) scatter characteristics (R1). (b) Lin-negative but HLA-DR-positive cells were gated on region R2. (c and d) Gates R1 and R2 were selected, and mDCs were identified as Lin negative, HLA-DR and CD11c-positive (R3) (c), while pDCs were identified as Lin negative, HLA-DR and CD123 positive (R3) (d).
FIG. 2.
FIG. 2.
The frequencies and absolute numbers of myeloid DCs (a and b) and plasmacytoid DCs (c and d) from subject (•) and control (○) neonates in different age groups plotted from the data from the cytometric analysis. Each dot represents a single donor, and the horizontal bars represent the means. There were no significant differences between children from chronically HBV-infected mothers and controls in all age groups. mDC and pDC frequencies and numbers were significantly lower at birth than for 1- and 6-month-old neonates, independent of maternal HBV status. *, P < 0.05 between groups; **, P < 0.005 between groups; ***, P < 0.0005 between groups.
FIG. 3.
FIG. 3.
IFN-α production from PBMCs in subject (•) and control (○) neonates after stimulation with R848 and/or RV1b. Each dot represents a single donor, and the horizontal bars represent the means. *, P < 0.05 between groups; **, P < 0.005 between groups.
FIG. 4.
FIG. 4.
IFN-α production from CB pDCs (a) and expression of costimulatory molecules (b to e) in subject (•) and control (○) neonates after stimulation with R848 and/or RV1b. Each dot represents a single donor, and the horizontal bars represent the means. No statistically significant differences were observed among the subjects and controls under similar conditions. Medium, nonstimulated CB pDCs.
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