Role of toll-like receptor 4 in protection by bacterial lipopolysaccharide in the nasal mucosa of atopic children but not adults.
BACKGROUND
Exposure to bacterial products in early life could protect against development of atopy. We examined the effect of bacterial lipopolysaccharide on allergic inflammation and expression of cytokines and lipopolysaccharide receptor (toll-like receptor 4 TLR4) in nasal mucosa of 15 atopic children and ten atopic adults.


METHODS
Explanted mucosa was cultured with allergen with or without lipopolysaccharide (0.1 mg/L) for 24 h. Immunocytochemistry and in-situ hybridisation were used to phenotype the cells and cytokines.


RESULTS
In explants from atopic children, lipopolysaccharide prevented allergen-induced T-helper type 2 (Th2) inflammation and upregulated Th1 cytokine reactivity and expression. These effects were blocked by antibody to interleukin 10. In children but not in adults, lipopolysaccharide caused increases of three times in T-cell reactivity, five times in T-cell proliferation, and four times in expression of interleukin 10 compared with mucosa stimulated with allergen alone. This difference in response was mirrored by lipopolysaccharide-induced increases in TLR4 reactivity in children but not adults. TLR4 receptor was expressed by CD3-positive T cells, and TLR4-positive cells contained interleukin 10. Lipopolysaccharide increased expression of cells positive for both CD3 and TLR4; both TLR4 and interleukin 10; and both CD4 and CD25.


CONCLUSIONS
Lipopolysaccharide inhibits allergic inflammation in nasal mucosa of atopic children by skewing local immune responses from Th2 to Th1 and upregulating production of interleukin 10. These effects are mediated by TLR4. Our results emphasise an important difference between adults and children in their ability to respond to bacterial products. These differences could have a role in normal maturation of the immune system.
Tulic
Meri K
MK
Meakins-Christie Laboratories, Notre-Dame Hospital and Institut ORL de Montréal, Montréal, Quebec, Canada. merit@ichr.uwa.edu.au
Fiset
Pierre-Olivier
PO
Manoukian
John J
JJ
Frenkiel
Saul
S
Lavigne
François
F
Eidelman
David H
DH
Hamid
Qutayba
Q
D000328:Adult; D000485:Allergens / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism; D002675:Child, Preschool; D046508:Culture Techniques; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation; D008070:Lipopolysaccharides / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D000485:Allergens; D017252:CD3 Complex; D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C433788:lipopolysaccharide, E. coli O26-B6