Meri K Tulic1, Mylene Vivinus-Nébot2, Akila Rekima3, Samara Rabelo Medeiros4, Chrystelle Bonnart5, Haining Shi6, Allan Walker6, Raffaella Dainese7, Julien Boyer7, Nathalie Vergnolle5, Thierry Piche7, Valérie Verhasselt1. 1. Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France The International Inflammation 'in-FLAME' Network, Worldwide Universities Network. 2. Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France Department of Immunology, Hôpital Archet 1, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France. 3. Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France. 4. Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. 5. INSERM U1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France CNRS, U5282, Toulouse, France Université de Toulouse, Site Paul Sabatier (UPS), Toulouse, France. 6. Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA. 7. Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France Department of Gastroenterology and Nutrition, Hôpital Archet 2, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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Keywords:
EPITHELIAL PERMEABILITY; GASTROINTESTINAL IMMUNE RESPONSE; GASTROINTESTINAL TRACT; GUT IMMUNOLOGY; GUT INFLAMMATION
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