Structural similarities of human and mammalian lipocalins, and their function in innate immunity and allergy.
Owners and their domestic animals via skin shedding and secretions, mutually exchange microbiomes, potential pathogens and innate immune molecules. Among the latter especially lipocalins are multifaceted: they may have an immunomodulatory function and, furthermore, they represent one of the most important animal allergen families. The amino acid identities, as well as their structures by superposition modeling were compared among human lipocalins, hLCN1 and hLCN2, and most important animal lipocalin allergens, such as Can f 1, Can f 2 and Can f 4 from dog, Fel d 4 from cats, Bos d 5 from cow's milk, Equ c 1 from horses, and Mus m 1 from mice, all of them representing major allergens. The β-barrel fold with a central molecular pocket is similar among human and animal lipocalins. Thereby, lipocalins are able to transport a variety of biological ligands in their highly conserved calyx-like cavity, among them siderophores with the strongest known capability to complex iron (Fe(3+) ). Levels of human lipocalins are elevated in nonallergic inflammation and cancer, associated with innate immunoregulatory functions that critically depend on ligand load. Accordingly, deficient loading of lipocalin allergens establishes their capacity to induce Th2 hypersensitivity. Our similarity analysis of human and mammalian lipocalins highlights their function in innate immunity and allergy.
The interuniversity Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University Vienna, University Vienna, Vienna, Austria.|Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University Vienna, Vienna, Austria.
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Jensen-Jarolim
Biotechnology Department, Center for Plant Biotechnology and Genomics, ETSI Montes, Technical University of Madrid, Madrid, Spain.|Department of Natural Systems and Resources, ETSI Montes, Technical University of Madrid, Madrid, Spain.
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Pacios
The interuniversity Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University Vienna, University Vienna, Vienna, Austria.
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Bianchini
The interuniversity Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University Vienna, University Vienna, Vienna, Austria.
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Hofstetter
The interuniversity Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University Vienna, University Vienna, Vienna, Austria.
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http://orcid.org/0000-0001-5005-9228
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Roth-Walter
D000485:Allergens / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D007108:Immune Tolerance; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000276:immunology; D056747:Immunomodulation; D054834:Lipocalins / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000485:Allergens; D054834:Lipocalins; D007073:Immunoglobulin E
allergen; animal; canine; iron; lipocalin