Abstract
BackgroundToll like receptors (TLRs) are an important and evolutionary conserved class of pattern recognition receptors associated with innate immunity. The recognition of Gram-positive cell wall constituents strongly depends on TLR2. In order to be functional, TLR2 predominantly forms a heterodimer with TLR1 or TLR6 within specialized membrane microdomains, the lipid rafts. The membrane lipid composition and the physicochemical properties of lipid rafts are subject to modification by exogenous fatty acids. Previous investigations of our group provide evidence that macrophage enrichment with polyunsaturated fatty acids (PUFA) induces a reordering of lipid rafts and non-rafts based on the incorporation of supplemented PUFA as well as their elongation and desaturation products.MethodsIn the present study we investigated potential constraining effects of membrane microdomain reorganization on the clustering of TLR2 with its co-receptors TLR1 and TLR6 within lipid rafts. To this end, RAW264.7 macrophages were supplemented with either docosahexaenoic acid (DHA) or arachidonic acid (AA) and analyzed for receptor expression and microdomain localization in context of TLR stimulation.Results and ConclusionsOur analyses showed that receptor levels and microdomain localization were unchanged by PUFA supplementation. The TLR2 pathway, in contrast to the TLR4 signaling cascade, is not affected by exogenous PUFA at the membrane level.
Highlights
The innate immune system represents the first barrier against invading pathogenic agents
TLR1, TLR2, and TLR6 expression is hardly influenced by polyunsaturated fatty acids (PUFA) supplementation
The impact of macrophage supplementation with unsaturated fatty acids in the absence or presence of a TLR2 ligand on TLR1, TLR2, and TLR6 receptor expression was assessed by Droplet Digital PCR (ddPCR) on RNA level and by flow cytometry on protein level
Summary
The innate immune system represents the first barrier against invading pathogenic agents It is based on the recognition of pathogen-associated molecular patterns (PAMPs) by genetically invariant receptors. This allows the organism to react to microbial invasions immediately. In the present study we investigated potential constraining effects of membrane microdomain reorganization on the clustering of TLR2 with its coreceptors TLR1 and TLR6 within lipid rafts. To this end, RAW264.7 macrophages were supplemented with either docosahexaenoic acid (DHA) or arachidonic acid (AA) and analyzed for receptor expression and microdomain localization in context of TLR stimulation. The TLR2 pathway, in contrast to the TLR4 signaling cascade, is not affected by exogenous PUFA at the membrane level
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