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

Maren Krause,Andrea Wangorsch,Stefan Vieths,Martin Globisch,Frank Blanco-Pérez,Masako Toda,Thomas Henle,Ger Van Zandbergen,Stephan Scheurer,Peter Crauwels,Jonas Lidholm

doi:10.1038/s41598-021-89402-1

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.

Highlights

Accumulated evidence indicates that some proteins are capable of stimulating innate immunity
A previous study suggested that natural Ara h 1 activates human monocyte derived dendritic cells by binding DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) and thereby induces Th2 skewing of naive T c ells17. nAra h 1 carries high mannose (Man5GlcNAc2 and Man6GlcNAc2) and nonfucosylated complex N-glycans
The results indicate that nAra h 1 activates both human monocyte derived macrophage type 1 (hMDM1) and hMDM2, and the activation is not due to TLR4 engagement

Summary

Introduction

Accumulated evidence indicates that some proteins are capable of stimulating innate immunity. HMDM1 were characterized by their fried-egg shaped morphology and CD14+ MHCII+ CD163- phenotype, whereas anti-inflammatory hMDM2 were characterized by CD14+ MHCII+ CD163+ with more elongated cell bodies[25] Using such hMDM1 and hMDM2, we found that (i) nAra h 1 activates both macrophage phenotypes but via different receptors, (ii) DC-SIGN is likely not a major receptor for nAra h 1-mediated activation in the both phenotypes, and (iii) macrophage scavenger receptor class A type I (SR-AI) is involved in a recognition of Ara h 1 by hMDM2

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Conclusion