Lipid raft localization of TLR2 and its co-receptors is independent of membrane lipid composition

Christine Hellwing; Axel Schoeniger; Claudia Roessler; Anja Leimert; Julia Schumann

doi:10.7717/peerj.4212

Lipid raft localization of TLR2 and its co-receptors is independent of membrane lipid composition

PeerJ. 2018 Jan 5:6:e4212. doi: 10.7717/peerj.4212. eCollection 2018.

Authors

Christine Hellwing¹, Axel Schoeniger², Claudia Roessler¹, Anja Leimert¹, Julia Schumann¹

Affiliations

¹ Clinic for Anesthesiology and Surgical Intensive Care, University Hospital Halle (Saale), Halle (Saale), Germany.
² Institute of Biochemistry, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany.

Abstract

Background: Toll 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.

Methods: In 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 conclusions: Our 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.

Keywords: Lipid rafts; Macrophages; Membrane lipid composition; PUFA; TLR1; TLR2; TLR6.

Grants and funding

This work has been supported by a grant from Deutsche Forschungsgemeinschaft (DFG, http://www.dfg.de), grant number SCHU 2586/1-2. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.