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Treatment with helicobacter pylorI extract protects against allergic asthma and inflammatory bowel disease


Engler-Anders, Daniela. Treatment with helicobacter pylorI extract protects against allergic asthma and inflammatory bowel disease. 2015, University of Zurich, Faculty of Science.

Abstract

Helicobacter pylori is a gram negative bacterium that has been colonizing the human stomach for more than 60`000 years. Colonization rates have been decreasing during the last 60 years, probably due to better sanitation, smaller family size and frequent use of antibiotics. H. pylori infection is known to cause gastritis, peptic ulcer and adenocarcinoma, but recent epidemiological as well as animal studies suggest a protective role of H. pylori against allergic asthma and inflammatory bowel disease (IBD). Here we demonstrate that not only live infection but also regular treatment with H. pylori extract is sufficient to achieve protection against allergic asthma and inflammatory bowel disease. Experimental autoimmune encephalomyelitis and type 1 diabetes cannot be prevented by live H. pylori infection or extract treatment in murine models.
In an ovalbumin-induced asthma mouse model, weekly extract treatment from the neonatal period onwards as well as adult treatment is protective against airway hyperreactivity, lung inflammation and goblet cell metaplasia. This protection is mediated by IL-10, mainly derived from dendritic cells. Presumably from the CD103+ DC subpopulation or the plasmacytoid DCs, which are increased in protected lungs. IL-18, important for Treg induction, is also essential for extract-mediated asthma protection presumably independent of regulatory T cells. VacA and GGT are two important H. pylori factors, which have immunoregulatory functions. Regular treatment with the purified proteins is sufficient to protect against ovalbumin-induced asthma. The protection through VacA is also dependent on IL-10, and CD103+ DCs and pDCs are increased in protected lungs as well.
H. pylori live infection as well as extract treatment also protect from chronic DSS-induced colitis. The upregulation of mucin-2, which acts as a physical barrier and can induce tolerogenic signaling, is a likely mechanism of protection. Furthermore, the NLRP3 inflammasome, known to be important for intestinal homeostasis, is essential for extract-mediated protection against colitis.

Abstract

Helicobacter pylori is a gram negative bacterium that has been colonizing the human stomach for more than 60`000 years. Colonization rates have been decreasing during the last 60 years, probably due to better sanitation, smaller family size and frequent use of antibiotics. H. pylori infection is known to cause gastritis, peptic ulcer and adenocarcinoma, but recent epidemiological as well as animal studies suggest a protective role of H. pylori against allergic asthma and inflammatory bowel disease (IBD). Here we demonstrate that not only live infection but also regular treatment with H. pylori extract is sufficient to achieve protection against allergic asthma and inflammatory bowel disease. Experimental autoimmune encephalomyelitis and type 1 diabetes cannot be prevented by live H. pylori infection or extract treatment in murine models.
In an ovalbumin-induced asthma mouse model, weekly extract treatment from the neonatal period onwards as well as adult treatment is protective against airway hyperreactivity, lung inflammation and goblet cell metaplasia. This protection is mediated by IL-10, mainly derived from dendritic cells. Presumably from the CD103+ DC subpopulation or the plasmacytoid DCs, which are increased in protected lungs. IL-18, important for Treg induction, is also essential for extract-mediated asthma protection presumably independent of regulatory T cells. VacA and GGT are two important H. pylori factors, which have immunoregulatory functions. Regular treatment with the purified proteins is sufficient to protect against ovalbumin-induced asthma. The protection through VacA is also dependent on IL-10, and CD103+ DCs and pDCs are increased in protected lungs as well.
H. pylori live infection as well as extract treatment also protect from chronic DSS-induced colitis. The upregulation of mucin-2, which acts as a physical barrier and can induce tolerogenic signaling, is a likely mechanism of protection. Furthermore, the NLRP3 inflammasome, known to be important for intestinal homeostasis, is essential for extract-mediated protection against colitis.

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Additional indexing

Item Type:Dissertation
Referees:Müller Anne, Becher Burkhard, Rogler Gerhard, Taube Christian
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2015
Deposited On:06 May 2015 07:29
Last Modified:08 Dec 2017 12:56

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