TY - JOUR
T1 - Human monocyte-derived type 1 and 2 macrophages recognize Ara h 1, a major peanut allergen, by different mechanisms
AU - Krause, Maren
AU - Crauwels, Peter
AU - Blanco-Pérez, Frank
AU - Globisch, Martin
AU - Wangorsch, Andrea
AU - Henle, Thomas
AU - Lidholm, Jonas
AU - van Zandbergen, Ger
AU - Vieths, Stefan
AU - Scheurer, Stephan
AU - Toda, Masako
N1 - Funding Information:
We thank Dr. Stefan Schülke for helpful discussion. This study is supported by JSPS KAKENHI Grant Number 18H05998 and JSPS Core-to-Core Program Advanced Research Networks entitled “Establishment of international agricultural immunology research-core for a quantum improvement in food safety”.
Funding Information:
The authors declare following competing interests: Dr. Stefan Vieths reports personal fees from Schattauer Allergologie Handbuch, personal fees from Elsevier Nahrungsmittelallergien und Intoleranzen, personal fees from Karger Food Allergy: Molecular Basis and Clinical Practice, non-financial support from German Research Foundation, non-financial support from European Directorate for the Quality of Medicines and Health Care, non-financial support from European Academy of Allergy and Clinical Immunology, non-financial support from German Chemical Society (GDCh), non-financial support from AKM Allergiekongress, non-financial support from International Union of Immunological Societies, non-financial support from Spanish Society for Allergy and Clinical Immunology (SEAIC), outside the submitted work. Dr. Jonas Lidholm is an employee of Thermo Fisher Scientific.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-021-89402-1
DO - 10.1038/s41598-021-89402-1
M3 - Article
C2 - 33980880
AN - SCOPUS:85105785514
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 10141
ER -