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

University Children's Hospital Munich, Department of Pulmonary, LMU, Munich, Germany.
Respiratory research (Impact Factor: 3.09). 02/2006; 7(1):40. DOI: 10.1186/1465-9921-7-40
Source: PubMed


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.
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 3H-Thymidine uptake, cytokine concentrations determined by ELISA, mRNA expression of T cell markers by real-time RT-PCR.
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.
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.

Download full-text


Available from: Bianca Schaub,
  • Source
    • "However, although the expression levels of TLRs were relatively low in comparison to monocytes and DCs, the biological significance of TLRs expression on a variety of T cells was substantial [27, 34, 36– 44]. It has been shown that TLR2 and 4 were important for the regulation of Tregs [42] [43] [44]. More recently, we have shown that the soluble form of heat shock protein 60 induced by HBV-replicating hepatocytes could enhance the HBcAgspecific Il10 secreting activity of Tregs via TLR2 (Figure 2). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Innate and adaptive immune systems have important role in the pathogenesis of acute and chronic infection with hepatitis B virus (HBV). These immune responses are mediated through complex interactions between the innate immune response and adaptive immune response. Toll-like receptors (TLRs) are a family of innate immune-recognition receptors that recognize the molecular patterns associated with microbial pathogens. So far, TLR1 to 13 were found in human or mice and investigated to detect the target molecules and the downstream mechanisms of these unique systems. Stimulation by their ligands initiates the activation of complex networks of intracellular signaling transduction and innate and adaptive immune-related cells (NK, NK-T, monocytes, dendritic cells, T cells, B cells, and Tregs, etc.). However, reports on such relationships between HBV and TLRs have been relatively rare in comparison to those on HCV and TLRs, but have recently been increasing. Thus, a review of TLRs involved in the pathogenesis of HBV infection may be needed toward better understanding of the immunopathogenesis of HBV infection.
    Gastroenterology Research and Practice 11/2011; 2011(6037):810939. DOI:10.1155/2011/810939 · 1.75 Impact Factor
  • Source
    • "However, we found an inverse association between cesarean section and IL-13 (a Th2 cytokine) and differences in the association between specific microbes in maternal stool and secretion of IL-13 vs. IL-10 by CBMCs, suggesting that neonatal IL-10 was likely secreted by Tregs (a major source of this cytokine) [19-21,43]. Other studies have found increased secretion of IL-10 and IFN-γ by CBMCs in response to stimulation with LPS [44], peptidoglycan (a cell wall component of gram-positive bacteria) [45], and mycobacterial extract (PPD) [12]. Together with our findings, these results suggest that different microbial stimuli can impact specific subsets of T cells in the fetal immune system such as Th1 cells and T regulatory cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The mechanisms for the association between birth by cesarean section and atopy and asthma are largely unknown. To examine whether cesarean section results in neonatal secretion of cytokines that are associated with increased risk of atopy and/or asthma in childhood. To examine whether the association between mode of delivery and neonatal immune responses is explained by exposure to the maternal gut flora (a marker of the vaginal flora). CBMCs were isolated from 37 neonates at delivery, and secretion of IL-13, IFN-gamma, and IL-10 (at baseline and after stimulation with antigens [dust mite and cat dander allergens, phytohemagglutinin, and lipopolysaccharide]) was quantified by ELISA. Total and specific microbes were quantified in maternal stool. The relation between mode of delivery and cord blood cytokines was examined by linear regression. The relation between maternal stool microbes and cord blood cytokines was examined by Spearman's correlation coefficients. Cesarean section was associated with increased levels of IL-13 and IFN-gamma. In multivariate analyses, cesarean section was associated with an increment of 79.4 pg/ml in secretion of IL-13 by CBMCs after stimulation with dust mite allergen (P < 0.001). Among children born by vaginal delivery, gram-positive anaerobes and total anaerobes in maternal stool were positively correlated with levels of IL-10, and gram-negative aerobic bacteria in maternal stool were negatively correlated with levels of IL-13 and IFN-gamma. Cesarean section is associated with increased levels of IL-13 and IFN-gamma, perhaps because of lack of labor and/or reduced exposure to specific microbes (e.g., gram-positive anaerobes) at birth.
    Clinical and Molecular Allergy 02/2006; 4(1):13. DOI:10.1186/1476-7961-4-13 · 1.39 Impact Factor
  • Source

Show more