Dietary wheat amylase trypsin inhibitors exacerbate murine allergic airway inflammation
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Wheat amylase trypsin inhibitors (ATI) are dietary non-gluten proteins that activate the toll-like receptor 4 on myeloid cells, promoting intestinal inflammation.
Aim of the study
We investigated the effects of dietary ATI on experimental allergic airway inflammation.
Mice on a gluten and ATI-free diet (GAFD), sensitized with PBS or ovalbumin (OVA) and challenged with OVA, were compared to mice on a commercial standard chow, a gluten diet naturally containing ~ 0.75% of protein as ATI (G+AD), a gluten diet containing ~ 0.19% of protein as ATI (G−AD) and a GAFD with 1% of protein as ATI (AD). Airway hyperreactivity (AHR), inflammation in bronchoalveolar lavage (BAL) and pulmonary tissue sections were analyzed. Allergic sensitization was assessed ex vivo via proliferation of OVA-stimulated splenocytes.
Mice on a GAFD sensitized with PBS did not develop AHR after local provocation with methacholine. Mice on a GAFD or on a G−AD and sensitized with OVA developed milder AHR compared to mice fed a G+AD or an AD. The increased AHR was paralleled by increased BAL eosinophils, IL-5 and IL-13 production, and an enhanced ex vivo splenocyte activation in the ATI-fed groups.
Dietary ATI enhance allergic airway inflammation in OVA-challenged mice, while an ATI-free or ATI-reduced diet has a protective effect on AHR. Nutritional wheat ATI, activators of intestinal myeloid cells, may be clinically relevant adjuvants to allergic airway inflammation.
KeywordsAmylase trypsin inhibitors Gluten Wheat sensitivity Innate immunity Allergic airway inflammation
Allergic airway inflammation
Amylase trypsin inhibitor
Human lymphocyte antigen
Non-celiac (non-allergy) wheat sensitivity
This study was supported by Grants of the German Research Foundation (DFG Schu646/17-1) and by the Leibniz-Foundation (Project WheatScan).
VZ: study design; acquisition of data; analysis and interpretation of data; drafting and editing of the manuscript; statistical analysis. VR: acquisition of data and support during experiment and data acquisition/analysis (stimulation of splenocytes). JM and PS: acquisition of data and support during in-vivo experiments (lung measurements). KS and other authors: support in revising the manuscript. DS: study design; interpretation of data; study supervision; drafting and editing of the manuscript.
Compliance with ethical standards
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
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