MODULATION OF ALLERGIC LUNG DISEASE BY RECOMBINANT BACILLUS CALMETTE GUERIN EXPRESSING A FRAGMENT FROM PERTUSSIS TOXIN

• Grant number: 12/00016-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2012
• End date: November 30, 2013
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Momtchilo Russo
• Grantee: Karina Mendes Melchuna
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 09/07208-0 - Modulation of allergic lung inflammation by adjuvants or by immunological tolerance, AP.TEM

Abstract

Asthma is a chronic lung disease characterized by bronchial hyperreactivity, eosinophilic airway inflammation, and high titers of immunoglobulin (Ig)-E. Epidemiological studies have shown the prevalence of allergic diseases, including asthma, is on the rise. One of the accepted explanations for this phenomenon is the Hygiene Hypothesis, in which the lower exposure to infectious disease, the overuse of antibiotics and the mass vaccination would facilitate the occurrence of allergies. The proposed immunological mechanisms to explain this phenomenon preconizes that the absence of microbial stimuli could interfere with T helper-type response or with the development of regulatory mechanisms. Previous work performed by Russo et al. at the University of São Paulo characterized the immune response induced by mycobacterium strains in a murine model of allergic asthma. The strains used were wild BCG Moreau, and recombinant BCG, which expresses the pertussis toxin subunit S1 genetically detoxified (rBCG-S1PT). It was shown that rBCG-S1PT was more effective in suppressing allergic parameters such a bronchial hyperreactivity, lung eosinophilia, secretion of mucus, and type-2 citokines (IL4, IL-5, and IL-13) in the broncho-alveolar lavage (BAL). The suppression of allergic response was associated with the production IFN- ³ in the lung with increased expression of T-bet transcript factor and decreased expression of GATA-3. The present work aims to evaluate the therapeutic/treatment effect of rBCG-S1PT administered by different routes in animals with established asthma, dissecting the possible regulatory mechanisms of rBCG-S1PT infection on chemokines, citokines and Th2 cells.