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Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis

Frei, Remo and Ferstl, Ruth and Roduit, Caroline and Ziegler, Mario and Schiavi, Elisa and Barcik, Weronika and Rodriguez-Perez, Noelia and Wirz, Oliver F. and Wawrzyniak, Marcin and Pugin, Benoit and Nehrbass, Dirk and Jutel, Marek and Smolinska, Sylwia and Konieczna, Patrycja and Bieli, Christian and Loeliger, Susanne and Waser, Marco and Pershagen, Göran and Riedler, Josef and Depner, Martin and Schaub, Bianca and Genuneit, Jon and Renz, Harald and Pekkanen, Juha and Karvonen, Anne M. and Dalphin, Jean-Charles and van Hage, Marianne and Doekes, Gert and Akdis, Mübeccel and Braun-Fahrländer, Charlotte and Akdis, Cezmi A. and von Mutius, Erika and O'Mahony, Liam and Lauener, Roger P. and Prevention of Allergy Risk factors for Sensitization in Children, and Anthroposophic Lifestyle study group, and Protection Against Allergy Study in Rural Environments /Mechanis, . (2018) Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis. Journal of Allergy and Clinical Immunology, 141 (1). 382-390.e7.

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Abstract

Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease.; We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role.; Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice.; In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17+ T-cell numbers and supported differentiation of regulatory T cells.; In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Environmental Exposures and Health > Physical Hazards and Health (Röösli)
UniBasel Contributors:Waser, Marco and Braun-Fahrländer, Charlotte
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0091-6749
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:14 Sep 2018 12:26
Deposited On:02 Feb 2018 14:06

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