Reduced membrane bound CD14 expression in the cord blood of infants with a family history of allergic disease.
BACKGROUND
Infants at increased risk of allergic disease have altered immune function at birth, but the specific immune changes described differ between studies and their precise nature is not well defined. Changes affecting innate immune responses may be particularly important in allergic disease pathogenesis.


OBJECTIVE
We investigated whether inherited risk of allergic disease is associated with altered markers of innate immunity, T cell regulation or dendritic cell (DC) percentage in human newborns.


METHODS
Cord blood was collected from infants at low risk (no parent affected by allergic disease, n=14), intermediate risk (one affected parent, n=54) or high risk (two affected parents, n=25) of developing allergic disease. Cord blood mononuclear cells were cultured with ovalbumin (OVA), lipopolysaccharide, lipoteichoic acid (LTA), heat-killed lactobacillus, alpha-CD3 or medium alone. Cells were analysed by flow cytometry for expression of CD14, FoxP3 and DC percentage, and by real-time RT-PCR for TLR2 and TLR4 expression in infants at intermediate or high risk of allergic disease.


RESULTS
Infants at high risk of allergic disease had reduced percentage of CD14(+) monocytes (P=0.01) and reduced CD14 mean fluorescence intensity (P=0.01) in uncultured mononuclear cells. They also had decreased DC percentage in mononuclear cells cultured with OVA (P=0.04), lipopolysaccharide (P=0.01), LTA (P=0.02) and alpha-CD3 (P=0.03) as compared with infants at intermediate or low risk of allergic disease. No relationship was seen between risk of allergic disease and TLR2 or TLR4 expression, or FoxP3 expression in cultured cells.


CONCLUSIONS
Infants with a biparental history of allergic disease have altered markers of innate immunity at birth, with reduced expression of membrane bound CD14 and consequently reduced in vitro development of DCs. Further work is needed to understand the role that these alterations play in the pathogenesis of allergic disease, and whether interventions to up-regulate fetal CD14 expression can prevent allergic disease.
Boyle
R J
RJ
Allergy and Immune Disorders, Murdoch Children's Research Institute, University of Melbourne, Parkville, Vict., Australia.
Morley
R
R
Mah
L-J
LJ
Kivivuori
S
S
Tang
M L-K
ML
D000328:Adult; D001800:Blood Specimen Collection; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D015331:Cohort Studies; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000097:blood* / Q000276:immunology*; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000097:blood* / Q000378:metabolism*; D008297:Male; D010865:Pilot Projects; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D015854:Up-Regulation / Q000276:immunology
D018950:Lipopolysaccharide Receptors