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

Frei, Remo; Ferstl, Ruth; Roduit, Caroline; Ziegler, Mario; Schiavi, Elisa; Barcik, Weronika; Rodríguez-Pérez, Noelia; Wirz, Oliver F.; Wawrzyniak, Marcin; Pugin, Benoı̂t; Nehrbass, Dirk; Jutel, Marek; Smolińska, Sylwia; Konieczna, Patrycja; Bieli, Christian; Loeliger, Susanne; Waser, Marco; Pershagen, Göran; Riedler, Josef; Depner, Martin; Schaub, Bianca; Genuneit, Jon; Renz, Harald; Pekkanen, Juha; Karvonen, Anne M.; Dalphin, Jean‐Charles; Hage, Marianne van; Doekes, Gert; Akdiş, Mübeccel; Braun‐Fahrländer, Charlotte; Akdiş, Cezmi A.; Mutius, Erika von; O’Mahony, Liam; Lauener, Roger

doi:10.1016/j.jaci.2017.04.051

Cited by 45 publications

(51 citation statements)

References 49 publications

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“…PBS buffer was used as a control, since free Neu5Gc would not completely inhibit the diverse reactivities of such antibodies given the potential complexity of Neu5Gc‐antigens on EC. In addition, recent data suggest that Neu5Gc itself may have a direct biological effect on human cells . Details of ECs stimulation procedures are given in the legend of Table S2.…”

Section: Methodsmentioning

confidence: 99%

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Elicited and pre‐existing anti‐Neu5Gc antibodies differentially affect human endothelial cells transcriptome

Berre

Danger

et al. 2019

Xenotransplantation

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Humans cannot synthesize N‐glycolylneuraminic acid (Neu5Gc) but dietary Neu5Gc can be absorbed and deposited on endothelial cells (ECs) and diet‐induced anti‐Neu5Gc antibodies (Abs) develop early in human life. While the interaction of Neu5Gc and diet‐induced anti‐Neu5Gc Abs occurs in all normal individuals, endothelium activation by elicited anti‐Neu5Gc Abs following a challenge with animal‐derived materials, such as following xenotransplantation, had been postulated. Ten primary human EC preparations were cultured with affinity‐purified anti‐Neu5Gc Abs from human sera obtained before or after exposure to Neu5Gc‐glycosylated rabbit IgGs (elicited Abs). RNAs of each EC preparation stimulated in various conditions by purified Abs were exhaustively sequenced. EC transcriptomic patterns induced by elicited anti‐Neu5Gc Abs, compared with pre‐existing ones, were analyzed. qPCR, cytokines/chemokines release, and apoptosis were tested on some EC preparations. The data showed that anti‐Neu5Gc Abs induced 967 differentially expressed (DE) genes. Most DE genes are shared following EC activation by pre‐existing or anti‐human T‐cell globulin (ATG)‐elicited anti‐Neu5Gc Abs. Compared with pre‐existing anti‐Neu5Gc Abs, which are normal component of ECs environment, elicited anti‐Neu5Gc Abs down‐regulated 66 genes, including master genes of EC function. Furthermore, elicited anti‐Neu5Gc Abs combined with complement‐containing serum down‐regulated most transcripts mobilized by serum alone. Both types of anti‐Neu5Gc Abs‐induced a dose‐ and complement‐dependent release of selected cytokines and chemokines. Altogether, these data show that, compared with pre‐existing anti‐Neu5Gc Abs, ATG‐elicited anti‐Neu5Gc Abs specifically modulate genes related to cytokine responses, MAPkinase cascades, chemotaxis, and integrins and do not skew the EC transcriptome toward a pro‐inflammatory profile in vitro.

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Section: Methodsmentioning

confidence: 99%

“…In addition, recent data suggest that Neu5Gc itself may have a direct biological effect on human cells. 19 Details of ECs stimulation procedures are given in the legend of Table S2. When mentioned, human pooled sera (dilution of 1:2, 50% of well volume) or TNFα (500 U/mL) were added to the culture medium.…”

Section: Endothelial Cell Stimulationmentioning

confidence: 99%

Elicited and pre‐existing anti‐Neu5Gc antibodies differentially affect human endothelial cells transcriptome

Berre

Danger

et al. 2019

Xenotransplantation

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“…A recent report found that N‐glycolylneuraminic acid (Neu5Gc), a sialic acid found in non‐human mammalian glycoproteins but absent in bacteria, is associated with lower rates of asthma and wheezing in farm children. Levels of anti‐Neu5Gc IgG antibodies correlated positively with living on a farm, and Neu5Gc exerted anti‐inflammatory effects in mouse models of airway inflammation …”

Section: Role Of Innate Immunity In Asthma Protectionmentioning

confidence: 97%

“…Levels of anti-Neu5Gc IgG antibodies correlated positively with living on a farm, and Neu5Gc exerted anti-inflammatory effects in mouse models of airway inflammation. 86…”

Section: Hdm-and Ova-induced Ahr and Bal Eosinophilia As Effectively Asmentioning

confidence: 99%

The role of innate immunity in asthma development and protection: Lessons from the environment

Pivniouk

Gimenes-Júnior

Honeker

et al. 2020

Clin Experimental Allergy

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Asthma, a complex, chronic disease characterized by airway inflammation, hyperresponsiveness and remodelling, affects over 300 million people worldwide. While the disease is typically associated with exaggerated allergen‐induced type 2 immune responses, these responses are strongly influenced by environmental exposures that stimulate innate immune pathways capable of promoting or protecting from asthma. The dual role played by innate immunity in asthma pathogenesis offers multiple opportunities for both research and clinical interventions and is the subject of this review.

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“…Zudem konnte nachgewiesen werden, dass auch nicht bakterielle Komponenten (z. B. N-Glycolylneuraminsäure) protektiv bei diesen Kindern wirken [9].…”

Section: Merkeunclassified

Obstruktive Lungenerkrankungen im Kindesalter

Tenbrock¹

2019

Pädiatrie up2date

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Obstruktive Lungenerkrankungen gehören zu den häufigsten Erkrankungen im Kindesalter überhaupt und umfassen ein ganzes Spektrum von Entitäten. Differenzialdiagnosen, Pathogenese, Diagnostik und Therapiemöglichkeiten von der Bronchiolitis im frühen Säuglingsalter über obstruktive Bronchitiden bei Kleinkindern bis hin zum großen Thema Asthma bronchiale, dies alles stellt dieser Beitrag kompakt vor.

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

Abstract: In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.

Cited by 45 publications

References 49 publications

Elicited and pre‐existing anti‐Neu5Gc antibodies differentially affect human endothelial cells transcriptome

Elicited and pre‐existing anti‐Neu5Gc antibodies differentially affect human endothelial cells transcriptome

The role of innate immunity in asthma development and protection: Lessons from the environment

Obstruktive Lungenerkrankungen im Kindesalter

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