Recognition of the Major Cat Allergen Fel d 1 through the Cysteine-rich Domain of the Mannose Receptor Determines Its Allergenicity

Emara, Mohamed; Royer, Pierre‐Joseph; Abbas, Zaigham; Sewell, Herb F.; Mohamed, Gihan Gebriel; Singh, Sonali; Peel, Samantha; Fox, Jane; Shakib, F; Martı́nez-Pomares, Luisa; Ghaemmaghami, Amir M.

doi:10.1074/jbc.m111.220657

Cited by 64 publications

(76 citation statements)

References 57 publications

(54 reference statements)

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“…Recently, it has been shown that the mannose receptor plays a major role in internalization of Fel d 1 by human and mouse antigen-presenting cells. 29 Determination of the carbohydrate composition of Ory c 3 will allow further comparison with Fel d 1 and allow us to carry out similar experiments to confirm the putative uptake mechanism by the mannose receptor.…”

Section: Discussionmentioning

confidence: 97%

Identification and isolation of a Fel d 1–like molecule as a major rabbit allergen

Hilger¹,

Kler²,

Arumugam³

et al. 2014

Journal of Allergy and Clinical Immunology

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Section: Discussionmentioning

confidence: 97%

Identification and isolation of a Fel d 1–like molecule as a major rabbit allergen

Hilger¹,

Kler²,

Arumugam³

et al. 2014

Journal of Allergy and Clinical Immunology

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“…9 Also, previous work has suggested that MRC1 on DCs mediates the uptake of diverse native allergens and determination of allergen-induced T-cell polarization. 4 In particular, MRC1-mediated Bla g 2 uptake on DCs is through the C-type lectin-like carbohydrate recognition domains 4 to 7. 5 In this study we observed a significant reduction in cockroach allergen uptake in Mrc1 −/− compared with WT mice, with a large number of macrophages that were colocalized with the inhaled cockroach allergen in the lungs of WT mice.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 MRC1 contains 8 C-type lectin–like domains and acts as a phagocytic receptor for bacteria, fungi, parasites, viruses, and allergens. 2–4 MRC1 has been suggested to mediate allergic sensitization and asthma to multiple glycoallergens, 4,5 including cockroach allergens. In fact, sensitization to cockroach allergens has been identified as one of the strongest risk factors for the development of asthma.…”

mentioning

confidence: 99%

Mannose receptor modulates macrophage polarization and allergic inflammation through miR-511-3p

Zhou

Danh

Ishmael

et al. 2018

Journal of Allergy and Clinical Immunology

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Background Mannose receptor (MRC1/CD206) has been suggested to mediate allergic sensitization and asthma to multiple glycoallergens, including cockroach allergens. Objective We sought to determine the existence of a protective mechanism through which MRC1 limits allergic inflammation through its intronic miR-511-3p. Methods We examined MRC1-mediated cockroach allergen uptake by lung macrophages and lung inflammation using C57BL/6 wild-type (WT) and Mrc1−/− mice. The role of miR-511-3p in macrophage polarization and cockroach allergen–induced lung inflammation in mice transfected with adeno-associated virus (AAV)–miR-511-3p (AAV– cytomegalovirus–miR-511-3p–enhanced green fluorescent protein) was analyzed. Gene profiling of macrophages with or without miR-511-3p overexpression was also performed. Results Mrc1−/− lung macrophages showed a significant reduction in cockroach allergen uptake compared with WT mice, and Mrc1−/− mice had an exacerbated lung inflammation with increased levels of cockroach allergen–specific IgE and TH2/TH17 cytokines in a cockroach allergen–induced mouse model compared with WT mice. Macrophages from Mrc1−/− mice showed significantly reduced levels of miR-511-3 and an M1 phenotype, whereas overexpression of miR-511-3p rendered macrophages to exhibit a M2 phenotype. Furthermore, mice transfected with AAV–miR-511-3p showed a significant reduction in cockroach allergen–induced inflammation. Profiling of macrophages with or without miR-511-3p overexpression identified 729 differentially expressed genes, wherein expression of prostaglandin D2 synthase (Ptgds) and its product PGD2 were significantly downregulated by miR-511-3p. Ptgds showed a robust binding to miR-511-3p, which might contribute to the protective effect of miR-511-3p. Plasma levels of miR-511-3p were significantly lower in human asthmatic patients compared with nonasthmatic subjects. Conclusion These studies support a critical but previously unrecognized role of MRC1 and miR-511-3p in protection against allergen-induced lung inflammation.

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“…MR-deficient animals sensitized with cat dander and purified Fel d 1 produce less total IgE and Fel d 1-specific IgE and IgG1 [31]. These in vivo results are a likely consequence of the fact that the main allergen used, Fel d 1, bears sulfated glycans and specifically binds to the CR domain of MR [31], and that priming took place in the peritoneal cavity, where MR is expressed by resident DCs [51]. No information regarding the presence of additional MR ligands in the cat dander extract is available.…”

Section: Contribution Of Mr To Diseasementioning

confidence: 99%

The mannose receptor

Martı́nez-Pomares

2012

Journal of Leukocyte Biology

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The MR is a highly effective endocytic receptor with a broad binding specificity encompassing ligands of microbial and endogenous origin and a poorly characterized ability to modulate cellular activation. This review provides an update of the latest developments in the field. It discusses how MR biology might be affected by glycosylation and proteolytic processing, MR involvement in antigen delivery, and the potential contribution of MR to T cell differentiation and cellular activation. Further understanding of these areas will, no doubt, inform the design of novel, therapeutic tools for improved vaccination, control of inflammation, and tumor chemotherapy, which will benefit from exploiting MR-efficient internalization properties and unique pattern of expression.

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Recognition of the Major Cat Allergen Fel d 1 through the Cysteine-rich Domain of the Mannose Receptor Determines Its Allergenicity

Cited by 64 publications

References 57 publications

Identification and isolation of a Fel d 1–like molecule as a major rabbit allergen

Identification and isolation of a Fel d 1–like molecule as a major rabbit allergen

Mannose receptor modulates macrophage polarization and allergic inflammation through miR-511-3p

The mannose receptor

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