Protection from allergy by a novel synthetic lipopeptide

Growing up on a farm provides protection from developing allergies. One explanation for this observation is given by the „hygiene hypothesis“, which states that the prevalence of allergies is increasing due to reduced risk of infection. In a mouse model of allergy and asthma, we have shown previously that extracts of cowshed dust extract (CDE) from traditional farms protect mice from allergy. Moreover, our study revealed that LPS was not responsible for the effect of CDE. It was also shown that prolonged exposure of bone-marrow derived dendritic cells (BMDCs) to CDE reduced their capacity to induce allergy when given to mice intranasally. By using TLR2 transfected HEK293 cells, we found that TLR2 ligands are also present in CDE. We asked whether TLR2 ligands mediate a protective effect as well. To produce a synthetic, highly active TLR2 ligand, 13 amino acids of the lipoprotein Germination protein D (GerD) of Bacillus cereus were fused to a triacyllipid. In a mouse model of allergic asthma, we could show that this GerD-TLR2 ligand prevented mice from airway hyperresponsiveness and lung eosinophilia, and reduced TH2 cytokines. Furthermore we examined the protective effect of the GerD-TLR2 ligand in an airway sensitization model using OVA pulsed BMDCs. We have first hints that it can protect from allergy by reducing sensitizing capacity of BMDCs, and we saw for the first time that the protective effect of CDE disappeared when BMDCs were generated from TLR2 deficient mice. Interestingly, the GerD-TLR2 ligand induced only marginal production of proinflammatory cytokines and no signs of toxicity in vivo. Therefore it might be a promising candidate for therapeutic use.