Neonatal immune responses to TLR2 stimulation: Influence of maternal atopy on Foxp3 and IL-10 expression

Neonatal immune responses to TLR2 stimulation: Influence of maternal atopy on Foxp3 and IL-10 expression

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vor 18 Jahren
Background: Maternal atopic background and stimulation of the
adaptive immune system with allergen interact in the development of
allergic disease. Stimulation of the innate immune system through
microbial exposure, such as activation of the innate Toll-like-
receptor 2 (TLR2), may reduce the development of allergy in
childhood. However, little is known about the immunological effects
of microbial stimulation on early immune responses and in
association with maternal atopy. Methods: We analyzed immune
responses of cord blood mononuclear cells ( CBMC) from 50 healthy
neonates ( 31 non-atopic and 19 atopic mothers). Cells were
stimulated with the TLR2 agonist peptidoglycan (Ppg) or the
allergen house dust mite Dermatophagoides farinae (Derf1), and
results compared to unstimulated cells. We analyzed lymphocyte
proliferation and cytokine secretion of CBMC. In addition, we
assessed gene expression associated with T regulatory cells
including the transcription factor Foxp3, the
glucocorticoid-induced TNF receptor ( GITR), and the cytotoxic
lymphocyte antigen 4 (CTLA4). Lymphocyte proliferation was measured
by H-3-Thymidine uptake, cytokine concentrations determined by
ELISA, mRNA expression of T cell markers by real-time RT-PCR.
Results: Ppg stimulation induced primarily IL-10 cytokine
production, in addition to IFN-gamma, IL-13 and TNF-alpha
secretion. GITR was increased following Ppg stimulation ( p =
0.07). Ppg- induced IL-10 production and induction of Foxp3 were
higher in CBMC without, than with maternal atopy ( p = 0.04, p =
0.049). IL-10 production was highly correlated with increased
expression of Foxp3 ( r = 0.53, p = 0.001), GITR ( r = 0.47, p =
0.004) and CTLA4 ( r = 0.49, p = 0.003), independent of maternal
atopy. Conclusion: TLR2 stimulation with Ppg induces IL-10 and
genes associated with T regulatory cells, influenced by maternal
atopy. Increased IL-10 and Foxp3 induction in CBMC of non-atopic
compared to atopic mothers, may indicate an increased capacity to
respond to microbial stimuli.

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