.The influence of asthma on the mouse ability to control the intranasal infection by the bacteria Brucella melitensis

Traduction de l'intitulé de la thèse: L'influence de l'asthme sur la capacité de la souris à contrôler l'infection intranasale par la bactérie Brucella melitensis
  • Georges Potemberg

Student thesis: Master typesMaster en biochimie et biologie moléculaire et cellulaire

Résumé

Brucella spp. are facultative intracellular bacterial pathogens responsible for brucellosis, a worldwide zoonosis that causes abortion in domestic animais and a chronic febrile disease associated with serious complications in humans. The human brucellosis is mainly transmitted through the consumption of contaminated food or by the inhalation of aerosols. There is currently no approved vaccine against human brucellosis and antibiotic therapy is long and costly. The furtiveness seems to be the main strategy for Brucella to evade the immune system and to persist in the host. In contrast to other causative agents of granulomatous diseases such as Mycobacterium tuberculosis, the agent of tuberculosis, Brucella is not able to persist at high levels in the lungs following an intranasal (IN) infection . A previous study suggest that THl and Th17 mediated immune response are implicated in the control of Brucella in the lungs. Asthma is an hypersensibility of the immune system to environmental antigens called allergens. This disorder displays an important inflammatory state of the lungs tissue induced by a T 82 immune response. Among the most frequent allergens there are the ho use dust mites allergens. The incidence of asthma has significantly increased worldwide since the 1970s.
According to the WHO, in 2011 , almost 300 million people were affected by asthma. In order to define the parameters affecting this protective immune control, we used a cross-pathology mode! implicating house dust mites (HDM)-induced allergie asthma as chronic bystander pathology. We induced asthma by repeated IN injections with HDM extract several weeks before the IN infection with Brucella melitensis. We demonstrated that the HDM-induced allergie asthma phenotype compromises the ability of mice to control the intranasal infection with Brucella melitensis. The Brucella burden was significantly augmented of more than 10 folds in the lungs of asthmatic mice. The asthma also increases the persistence of Brucella in the lungs for a longer time. This phenomenon is strictly dependent of allergie asthma-induced T82 environment as it is absent in STAT-6 deficient mice that are notable to develop a Ttt2 response. Our preliminary data suggest that asthma does not inhibit the development of a protective T 8 1 immune response but rather promotes the replication of Brucella inside the alveolar macrophages of the lungs.
la date de réponse2015
langue originaleAnglais
L'institution diplômante
  • Universite de Namur
SuperviseurJEAN-JACQUES LETESSON (Promoteur) & Eric MURAILLE (Copromoteur)

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