Background Regulatory T cells (Treg) play a crucial role in maintaining immune homeostasis and self-tolerance. dendritic cells (DCs) individually and in co-cultures with Tregs. Results TLR2 agonists can directly provide a co-stimulatory signal inducing enhanced proliferation and cytokine production of naive CD4+ Teff 20(S)-NotoginsenosideR2 cells. With respect to cytokine production DCs appear to be most sensitive to low amounts of TLR agonists. Using wild type and TLR2-deficient cells in Treg suppression assays we accordingly show that all cells (e.g. Treg Teff cells and DCs) contributed to overcome Treg-mediated suppression of Teff cell proliferation. Furthermore while TLR2-stimulated Tregs readily lost their ability to suppress Teff cell proliferation cytokine production by Teff cells was still suppressed. Similar results were obtained upon stimulation with TLR2 ligand containing bacteria Legionella pneumophila. Conclusions These findings indicate that both synthetic and natural TLR2 agonists affect DCs Teff cells and Treg directly resulting in multi-modal modulation of Treg-mediated suppression of Teff cells. Moreover Treg-mediated suppression of Teff cell proliferation is usually functionally distinct from suppression of cytokine secretion. Background The immune system is usually of crucial importance to our health and survival. Faced with pathogenic threats from outside as well as the rise of cancer cells from within our immune defense must be able to cope with very diverse opponents. Mammals have developed a diverse set of receptors that sense components derived from pathogens and damaged cells. Amongst the best studied receptors are the so called pattern recognition receptors (PRR) like the Toll-like receptor (TLR) family members RIG-I-like receptor (RLR) family members and the NOD-like receptor (NLR) category of protein [1]. Generally engagement of the receptors on immune system cells results within their activation like improved antigen display inflammatory cytokine creation as well as the acquisition of immune system effector function [2]. Pathogen reputation through particular TLRs could be of essential importance for the induction of defensive immunity. For example TLR4-deficient mice are even more susceptible 20(S)-NotoginsenosideR2 for attacks with Neisseria meningitidis E. coli Haemophilus influenzae Salmonella enteritidis and Klebsiella pneumonia [3]. In this respect the immunological ramifications of TLR2 ligation are incredibly different set alongside the various other TLRs (evaluated by Netea et al [3]). First of all TLR2 20(S)-NotoginsenosideR2 continues to be reported to immediate the broadest repertoire of danger-associated molecular patterns from a big selection of pathogens including gram-positive and gram-negative bacterias fungi infections and parasites but also endogenous protein like Heat Surprise Proteins 60 (HSP60) [4]. This wide range of recognition could be explained with the heterodimerization of TLR2 with either TLR6 or TLR1. However the 20(S)-NotoginsenosideR2 latest publication from the TLR1/2 receptor-ligand crystal framework [5] in conjunction with the incredibly high affinity of TLR2 because of its lipoprotein ligands [6] escalates the possibility a amount of putative TLR2-ligands haven’t any intrinsic TLR2-activating capacities but had been actually polluted by lipoproteins [6]. Subsequently TLR2-deficient mice are much less vunerable to lethal attacks with Aspergillus fumigatus Yersinia enterocolitica or Candida albicans which is certainly on the other hand with e.g. TLR4-deficient mice [7]. In TLR2-lacking mice level of resistance to C. albicans is certainly mediated by a stronger Th1 response due to diminished production of IL-10 during the infectious challenge [8]. The unique functions of TLR2 and TLR4 in immunomodulation was further emphasized by PLA2B findings that TLR2-deficient mice experienced increased joint inflammation in preclinical rheumatoid arthritis (RA) models while TLR4-deficient mice were more resistant [9]. Interestingly the enhanced immunological responses in TLR2-deficient mice correlate with decreased numbers of Tregs in these mice [8]. Moreover C. albicans induced proliferation and survival of Tregs in a TLR2-dependent manner [8]. Different types of Tregs have been characterized and these Tregs are indispensable for the maintenance of immunologic self-tolerance and immune homeostasis [10]. The naturally occurring CD25+CD4+FoxP3+ Tregs are generated in the thymus and constitute about 5-15% of the peripheral CD4+ T cells in healthy animals and humans [11-13]. Once naturally occurring Tregs are activated via TCR-triggering they are able to actively suppress the function of multiple immune.