Human monocyte-derived type 1 and 2 macrophages recognize Ara h 1, a major peanut allergen, by different mechanisms

Abstract

Evidence has suggested that major peanut allergen Ara h 1 activates dendritic cells (DCs) via interaction with DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin), a C-type lectin receptor, and contributes to development of peanut allergy. Since macrophages, as well as DCs, play a crucial role in innate immunity, we investigated whether natural Ara h 1 (nAra h 1) activates two different subsets of macrophages, human monocyte derived macrophage type 1 (hMDM1: pro-inflammatory model) and type 2 (hMDM2: anti-inflammatory model). hMDM1 and hMDM2 predominantly produced pro-inflammatory cytokines (IL-6 and TNF-α) and an anti-inflammatory cytokine (IL-10) in response to nAra h 1, respectively. hMDM2 took up nAra h 1 and expressed DC-SIGN at higher levels than hMDM1. However, small interfering RNA knockdown of DC-SIGN did not suppress nAra h 1 uptake and nAra h 1-mediated cytokine production in hMDM2. Inhibitors of scavenger receptor class A type I (SR-AI) suppressed the response of hMDM2, but not of hMDM1, suggesting that SR-AI is a major receptor in hMDM2 for nAra h 1 recognition and internalization. nAra h 1 appears to exert stimulatory capacity on DC and macrophages via different receptors. This study advances our understanding how a major peanut allergen interacts with innate immunity.

The Impacts of Cholesterol, Oxysterols, and Cholesterol Lowering Dietary Compounds on the Immune System

“…Natural Ara h 1 carries high mannose (Man5GlcNAc2 and Man6GlcNAc2) and nonfucosylated complex N-glycans (Man4XylGlcNAc2 and Man3XylGlcNAc2) [ 207 ]. Studies have shown that such carbohydrate residues bind to DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) or Scavenger receptor A (SR-A) and thus activate human monocyte-derived DC and macrophages [ 208 , 209 ]. Beta-conglycinin also carries N-linked glycans comprising 77% mannose and 23% N-acetylglucosamine, and thus might have the intrinsic immunogenicity to stimulate macrophages and DCs like peanut 7S globulin [ 210 ].…”

Peanut allergen induces more serious allergic reactions than other allergens involving MAPK signaling pathways

“…8 At present, research on allergies caused by various food proteins mainly focuses on the mechanism of food allergies. 9,10 The difference and severity of allergy symptoms caused by these food proteins is still not well understood. Interestingly, Mondoulet et al studied CD62L + Tregs isolated from mice treated with milkepicutaneous immunotherapy (EPIT), and found that mice with CD62L + Treg transfer before peanut sensitization were protected from anaphylaxis as compared with an allergic group.…”