Lipids regulate the dynamics of early allergic inflammation towards grass pollen

Abstract

Nearly 30% of bronchial allergic asthma cases are induced by grass pollen. Research regarding allergy to pollen has focused on the study of proteins as allergens. However, apart from proteins, the pollen coat contains a large range of lipids. Previous reports showed that crude pollen-derived lipid extracts activated dendritic cells (DCs) and Natural Killer T (NKT) cells towards an allergic phenotype. However, the detailed structure-activity relationship between lipid classes and reactive immune cells in the context of allergic inflammation remains poorly understood. Hence, we aimed to isolate and characterize the chemical structures of the lipid classes present in Timothy grass (Phleum pratense) pollen and determine their role in allergic inflammation.

After extraction, separation on a silica column and HPLC fractionation, we isolated two main different lipid classes; namely lipid mediators and glycolipids. Their chemical structures were determined by GC-MS, Mass spectrometry and NMR analyses. The biological activity of lipids was tested in different murine and human cell-based systems using flow cytometry.

Lipid mediators enhanced IgE-dependent degranulation in murine Mast cells. And in DCs, lipid mediators selectively induced the upregulation of CD1d, likely preparing glycolipid-antigen presentation to NKT cells. Two additional fractions containing glycoglycero- and glycosphingolipids, induced the proliferation of murine NKT cells ex vivo. Finally, pollen-derived glycolipids also activated human peripheral-blood NKT and γδ-T cells.

Taken together, our results provide a defined structure-activity relationship for lipid classes from grass pollen in the process of early-effector allergic inflammation.