Interaction of Non-Specific Lipid-Transfer Proteins With Plant-Derived Lipids and Its Impact on Allergic Sensitization

Abstract

Non-specific lipid-transfer proteins (nsLTPs) represent a family of ubiquitous plant proteins belonging to the prolamin superfamily. nsLTPs are characterized by a globular α-helical structure stabilized by four disulfide bonds and a hydrophobic cavity which acts as ligand-binding site for a broad spectrum of lipids and hydrophobic molecules. nsLTPs are involved in membrane biogenesis and in the adaption of plants to abiotic and biotic stress. They display antimicrobial activity by the ability to permeabilize the cell membrane of phytopathogens. Moreover, in the presence of lipids, nsLTPs are suggested to activate the plant immune system by a receptor-dependent mechanism. Additionally, nsLTPs from pollen and plant-derived food, in particular type 1 nsLTPs (9 kDa), are described as potent allergens. Within the nsLTP family Pru p 3 from peach is the clinically most relevant allergen which can cause genuine food allergy and frequently elicits severe clinical reactions. So far, the allergenic properties of nsLTPs are attributed to both their low molecular mass and their high thermal and proteolytic stability which allow them to reach the immune system in a biological intact form. Recently, the interaction of nsLTPs with lipids has been suggested to increase their allergenic properties and to promote the allergic sensitization to these proteins. This review will summarize the current knowledge on diversity of lipid ligands of plant LTPs, and illustrate recent studies performed with allergenic nsLTPs to investigate the effect of lipid binding on the structural modification and IgE-binding properties of proteins, and finally the potential effect on the innate immune responses.

Keywords: (glycero)phospholipid; CD1d; allergen; fatty acid; invariant natural killer T cell; lipid; non-specific lipid-transfer protein.

Figure 1

Impact of lipid binding to non-specific lipid-transfer proteins (nsLTPs) on the IgE-reactivity and allergic sensitization. Lipid binding can affect gastrointestinal stability and IgE-reactivity of nsLTPs. Whether the altered IgE-reactivity upon lipid binding is accompanied by structural modification of the protein remains to be elucidated. Moreover, lipids can induce a cytokine- or CD1d-mediated activation of invariant natural killer T (iNKT) cells. Microbial lipids are sensed by pathogen recognition receptors (PRRs) on APCs (DC and Mϕ) and induce an IL-12-mediated activation of iNKT cells which is accompanied by INF-γ secretion. Other lipid ligands which are administrated to APCs in a complex with nsLTPs are internalized, loaded on CD1d, and presented to the TCR (Vα24/Jα18⁺ in humans) on iNKT cells. The CD1d-restricted activation of iNKT cells by nsLTP–lipid complexes is suggested to promote the allergic sensitization by inducing T_H2-cytokine secretion. In line with this, iNKT cells can promote airway hyperreactivity (AHR) in the presence of IL-25, IL-33, and TSLP. However, activated iNKT cells can display a T_H1- (INF-γ) and T_H2- (IL-5, IL-4, and IL-13) like plasticity and lipids can either promote or attenuate NLRP3 inflammasome activity and induce both pro- or anti-inflammatory cytokines.