Article

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: 3.38). 02/2006; 7(1):40. DOI: 10.1186/1465-9921-7-40
Source: PubMed

ABSTRACT 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

Full-text

Available from: Bianca Schaub, Aug 14, 2015
0 Followers
 · 
106 Views
  • 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; 2011:810939. DOI:10.1155/2011/810939 · 1.75 Impact Factor
  • Source
  • Source
Show more