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A novel synthetic lipopeptide is allergy‐protective by the induction of LPS ‐tolerance
Author(s) -
Stiehm M.,
Peters K.,
Wiesmüller K.H.,
Bufe A.,
Peters M.
Publication year - 2013
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12116
Subject(s) - lipopeptide , allergy , medicine , desensitization (medicine) , immunology , biology , bacteria , receptor , genetics
Summary Background Exposure to the environment of traditional farms can protect children from some allergic disease. Due to this exposure, TLR 2 expression in these children is increased. TLR 2 ligands derived from gram‐positive bacteria are found in the dust of these farms. Objectives We proved whether a synthetic lipopeptide binding to the TLR 1/2 heterodimer is able to protect from allergic disease in two different murine models of allergy. We also investigated the immunological mechanisms underlying the protective properties of the lipopeptide. Methods We synthesized a lipopeptide derived from a germination lipoprotein of Bacillus cereus ( LPG erD). We evaluated the immunomodulatory activity of LPG erD in a murine model of systemic sensitization ( OVA /Alum) and in a model in which mice were sensitized with OVA pulsed bone‐marrow‐derived dendritic cells ( BMDC s) via the airways. Furthermore, the induction of LPS tolerance was studied. Results Treatment of mice with LPGerD in a mouse model of asthma led to protection against sensitization and airway inflammation. Similarly, bone‐marrow‐derived dendritic cells (BMDCs) pre‐treated with LPGerD were not able to prime mice for allergic immune response. We observed that pre‐treatment with LPGerD led to the induction of a LPS‐tolerant state in BMDCs. These cells secreted markedly lower amounts of pro‐inflammatory cytokines upon LPS stimulation. Furthermore, we observed an up‐regulation of IRAK‐M mRNA in BMDCs pre‐treated with LPGerD. Conclusions and Clinical Relevance Our results suggest that induction of a LPS ‐tolerant state in antigen‐presenting cells ( APC s) may contribute to the protective effect of a farming environment. TLR 2 agonists similar to those appearing in cowshed dust extracts, such as our synthetic LPG erD, lead to the ignorance of the LPS stimulus, which is important for the activation of APC s to mount a Th2 immune response. This substance might be a promising candidate for allergy‐preventive treatments as LPG erD had only low pro‐inflammatory characteristics.