Presymptomatic differences in Toll-like receptor function in infants who have allergy.
BACKGROUND
Microbial exposure might play a key role in allergy development, but little is known about the role of Toll-like receptors (TLRs).


OBJECTIVE
This study explored the association between neonatal TLR microbial recognition/function, allergy risk (maternal allergy), and prospective allergy development.


METHODS
Cord blood mononuclear cells (n = 111) were cultured either alone or with optimal concentrations of TLR ligands: lipoteichoic acid (TLR2), polyinosinicpolycytidylic acid (TLR3), LPS with IFN-gamma (TLR4), flagellin (TLR5), imiquimod R837 (TLR7), or CpG (TLR9). Cytokine responses were assessed in relation to allergy risk (maternal allergy) and allergy outcomes (sensitization, food allergy, and atopic dermatitis) at 12 months of age.


RESULTS
Maternal allergy (n = 59) was associated with significantly higher neonatal IL-12 and IFN-gamma responses to TLR2, TLR3, and TLR4 activation, whereas TNF-alpha and IL-6 responses to TLR2, TLR4, and TLR5 activation were significantly higher in newborns who subsequently had allergic disease (n = 32). Notably, consistent with previous reports, newborns who had disease had lower T(H)1 IFN-gamma response to mitogens (PHA).


CONCLUSIONS
Allergic disease was associated with increased (rather than decreased) perinatal TLR responses. Further studies are needed to determine how these responses track in the postnatal period and whether this relative hyperresponsiveness is a product of intrauterine influences, including maternal atopy, functional genetic polymorphisms, or both.
School of Paediatrics and Child Health, University of Western Australia, Perth, Australia. sprescott@meddent.uwa.edu.au
Susan L
SL
Prescott
Paul
P
Noakes
Bonita W Y
BW
Chow
Liza
L
Breckler
Catherine A
CA
Thornton
Elysia M
EM
Hollams
May
M
Ali
Anita H J
AH
van den Biggelaar
Meri K
MK
Tulic
D000818:Animals; D000829:Animals, Domestic; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D007223:Infant; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D018811:Maternal Exposure; D009035:Mothers; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D012333:RNA, Messenger; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors