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Atopy affects LPS responsiveness and TLR-4 expression in children peripheral mononuclear cells

Background

Lipopolysaccharide (LPS) exposure in early life is associated with a lower incidence of atopy. We sought to determine whether atopy regulates TLR-4 expression and LPS-induced signal transduction on peripheral immune cells e.g. CD4 T ‘helper’ T cells, monocytes and B cells of a large pediatric cohort.

Methods

Over 350 subjects were recruited from the Pediatric Test Center of the Montreal Children’s Hospital and a questionnaire was administered to determine presence of a history of atopic diseases. 3-5cc of anti-coagulated blood was taken and peripheral blood mononuclear cells were cultured for up to 24h with IL-4 (13.5ng/ml) and/or LPS (up to 5µg/ml). We conducted flow cytometric analysis for surface TLR-4 expression, along with T ‘helper’ lymphocyte marker CD4, pan-B lymphocyte marker CD19, monocyte marker CD14, and for intracellular phosphorylated p44/p42 and p38 signaling molecules.

Results

Non-atopic monocytes prominently internalize TLR-4 and trigger signal transduction (e.g. phosphorylation of p44/p42 and of p38) upon LPS exposure. Such LPS responsiveness was strikingly impaired in monocytes from atopic children. Compared with monocytes, reduced proportions of CD4+High T ‘helper’ lymphocytes and CD19+ B cells express TLR-4. In T cells, TLR-4 expression varies with age (it peaks between 7-17 years of age) and atopy; atopic children display reduced TLR-4 expression compared with controls. Recombinant IL-4 also interferes with LPS signaling, and was found to differentially modulate TLR-4 expression in T ‘helper’, B lymphocytes and monocytes.

Conclusions

Peripheral TLR-4+ CD14+ CD4+Low monocytes may be used to discriminate between atopic and non-atopic children based on reduced LPS-induced signaling in atopic subjects. TLR-4 expression greatly varies with age and appears to be affected by both atopic status and IL-4. Our data suggest that atopy and Th2-type immune bias may impair TLR-4-mediated innate immune function during childhood and, therefore influence allergic disease manifestations.

Research funding sources

AllerGen NCE Inc., J.T. Costello Memorial Research Fund. Fonds de Recherche en Santé du Québec (FRSQ).

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Correspondence to D Préfontaine or BD Mazer.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Préfontaine, D., Banville-Langelier, A., Fiset, P. et al. Atopy affects LPS responsiveness and TLR-4 expression in children peripheral mononuclear cells. All Asth Clin Immun 6, P17 (2010). https://doi.org/10.1186/1710-1492-6-S1-P17

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Keywords

  • Peripheral Immune Cell
  • Innate Immune Function
  • Atopic Child
  • Lymphocyte Marker
  • Trigger Signal Transduction
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