Receptor Mediated Effects of Advanced Glycation End Products (AGEs) on Innate and Adaptative Immunity: Relevance for Food Allergy

Abstract

As of late, evidence has been emerging that the Maillard reaction (MR, also referred to as glycation) affects the structure and function of food proteins. MR induces the conformational and chemical modification of food proteins, not only on the level of IgG/IgE recognition, but also by increasing the interaction and recognition of these modified proteins by antigen-presenting cells (APCs). This affects their biological properties, including digestibility, bioavailability, immunogenicity, and ultimately their allergenicity. APCs possess various receptors that recognize glycation structures, which include receptor for advanced glycation end products (RAGE), scavenger receptors (SRs), galectin-3 and CD36. Through these receptors, glycation structures may influence the recognition, uptake and antigen-processing of food allergens by dendritic cells (DCs) and monocytes. This may lead to enhanced cytokine production and maturation of DCs, and may also induce adaptive immune responses to the antigens/allergens as a result of antigen uptake, processing and presentation to T cells. Here, we aim to review the current literature on the immunogenicity of AGEs originating from food (exogenous or dietary AGEs) in relation to AGEs that are formed within the body (endogenous AGEs), their interactions with receptors present on immune cells, and their effects on the activation of the innate as well as the adaptive immune system. Finally, we review the clinical relevance of AGEs in food allergies.

Investigation of the allergenicity alterations of shrimp tropomyosin as glycated by glucose and maltotriose containing advanced glycation end products

“…5,6 Previous investigations have demonstrated that AGEs (e.g., N ε -(carboxymethyl) lysine and CML) could serve as epitopes for activating the allergic reactions of immune cells via the receptor for advanced glycation end products (RAGE). [7][8][9] RAGE is an immunoglobulin superfamily element, a 45 kDa protein that appears on the surfaces of immune cells (e.g., mast cell and basophil) that induce allergic reactions. 10,11 The binding of AGEs to RAGE (the AGEs-RAGE axis) could trigger pro-inflammatory and pro-allergic cellular responses, which has been demonstrated in previous investigations.…”

Type 2 diabetes, gut microbiome, and systems biology: A novel perspective for a new era

“… 36 , 37 Due to a high-fat diet, these receptors are activated in response to microbial stimuli such as LPS, which is present on the membranes of gram-negative bacteria. 39 TLRs, specifically TLR-4, also interact with glycosylated serum proteins called advanced glycosylation end products (AGEs) 40 , 41 to activate the transcription of MAPKs and NF-κB. In turn, this last pathway acts as an enhancer of activated β-cells after activation by LPS.…”

“…As a consequence of this glycosylation, the production of AGEs is favored. 40 , 41 AGEs in macrophages can bind to TLR-4, which is overexpressed in T2D. Thus, TLR activation leads to a cascade of intracellular signaling mediated by NF-κB when it is translocated to the nucleus, and activates the transcription of genes coding for cytokines and inflammatory chemokines, including tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 8 (CXCL8).…”

The RAGE/DIAPH1 Signaling Axis & Implications for the Pathogenesis of Diabetic Complications

“…Spotlight on contributory roles for the AGEs in the pathogenesis of obesity and diabetic complications continues to grow [5]. Beyond the higher concentrations of the heterogenous groups of endogenously formed AGEs driven by hyperglycemia [6], exogenously derived AGEs, such as those imbibed through food, may play adjunctive roles in the pathogenesis of metabolic dysfunction [7]. Many of the endogenously generated AGE forms have also been detected in foods, such as the common and prevalent specific AGE, peptides and proteins modified by carboxymethyllysineAGE (CML-AGE), which are known ligands for the receptor for advanced glycation end-products (RAGE) [8,9].…”

“…Despite these considerations, the extent to which these food-derived AGEs are absorbed in their intact signal transduction-enabled forms, after gastrointestinal tract exposure to gastric acids and specific gut microbiota, as well as the mechanisms mediating absorption of these species across the gut, are yet to be fully clarified [6,13]. Furthermore, studies on the metabolic effects of high-vs. low-AGE diets are not conclusive.…”