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Original article
Presence of commensal house dust mite allergen in human gastrointestinal tract: a potential contributor to intestinal barrier dysfunction
  1. Meri K Tulic1,2,
  2. Mylene Vivinus-Nébot1,3,
  3. Akila Rekima1,
  4. Samara Rabelo Medeiros1,4,
  5. Chrystelle Bonnart5,6,7,
  6. Haining Shi8,
  7. Allan Walker8,
  8. Raffaella Dainese1,9,
  9. Julien Boyer1,9,
  10. Nathalie Vergnolle5,6,7,
  11. Thierry Piche1,9,
  12. Valérie Verhasselt1,2
  1. 1Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France
  2. 2The International Inflammation ‘in-FLAME’ Network, Worldwide Universities Network
  3. 3Department of Immunology, Hôpital Archet 1, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France
  4. 4Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
  5. 5INSERM U1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France
  6. 6CNRS, U5282, Toulouse, France
  7. 7Université de Toulouse, Site Paul Sabatier (UPS), Toulouse, France
  8. 8Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA
  9. 9Department of Gastroenterology and Nutrition, Hôpital Archet 2, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France
  1. Correspondence to Dr Meri K Tulic, Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Hôpital de l'Archet 1, Route Saint Antoine de Ginestière BP3079, 06202 Nice Cedex 03, France; meri.tulic{at}unice.fr Dr V Verhasselt, Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Hôpital de l'Archet 1, Route Saint Antoine de Ginestière BP3079, 06202 Nice Cedex 03, Nice, France; valerie.verhasselt{at}unice.fr

Abstract

Background Abnormal gut barrier function is the basis of gut inflammatory disease. It is known that house dust mite (HDM) aero-allergens induce inflammation in respiratory mucosa. We have recently reported allergen from Dermatophagoides pteronyssinus (Der p1) to be present in rodent gut.

Objective To examine whether Der p1 is present in human gut and to assess its effect on gut barrier function and inflammation.

Design Colonic biopsies, gut fluid, serum and stool were collected from healthy adults during endoscopy. Der p1 was measured by ELISA. Effect of HDM was assessed on gut permeability, tight-junction and mucin expression, and cytokine production, in presence or absence of cysteine protease inhibitors or serine protease inhibitors. In vivo effect of HDM was examined in mice given oral HDM or protease-neutralised HDM. Role of HDM in low-grade inflammation was studied in patients with IBS.

Results HDM Der p1 was detected in the human gut. In colonic biopsies from healthy patients, HDM increased epithelial permeability (p<0.001), reduced expression of tight-junction proteins and mucus barrier. These effects were associated with increased tumour necrosis factor (TNF)-α and interleukin (IL)-10 production and were abolished by cysteine-protease inhibitor (p<0.01). HDM effects did not require Th2 immunity. Results were confirmed in vivo in mice. In patients with IBS, HDM further deteriorated gut barrier function, induced TNF-α but failed to induce IL-10 secretion (p<0.001).

Conclusions HDM, a ubiquitous environmental factor, is present in the human gut where it directly affects gut function through its proteolytic activity. HDM may be an important trigger of gut dysfunction and warrants further investigation.

  • GASTROINTESTINAL IMMUNE RESPONSE
  • GASTROINTESTINAL TRACT
  • GUT IMMUNOLOGY
  • GUT INFLAMMATION
  • EPITHELIAL PERMEABILITY

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