Multifaceted effects of synthetic TLR2 ligand and Legionella pneumophilia on Treg-mediated suppression of T cell activation

TLR2 agonists can directly provide a co-stimulatory signal inducing enhanced proliferation and cytokine production of naive CD4+ Teff 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.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 functionally distinct from suppression of cytokine secretion.The immune system is 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, RIG-I-like receptor (RLR) family and the NOD-like receptor (NLR) family of proteins [1]. In general, engagement of these receptors on immune cells results in their activation, like enhanced antigen presentation, inflammatory cytokine production and the acquisition of immune effector function [2].Pathogen recognition through specific TLRs can be of crucial importance for the induction of protective immunity. For instance, TLR4-deficient mice are more susceptible for infection