Enhancement of Th1 Lung Immunity Induced by Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Attenuates Airway Allergic Disease

Author(s)

Christ, Ana P. ^[1] ; Rodriguez, Dunia ^[2] ; Bortolatto, Juliana ^[2] ; Borducchi, Erica ^[2] ; Keller, Alexandre ^[2] ; Mucida, Daniel ^[2] ; Silva, Joao S. ^[3] ; Leite, Luciana C. C. ^[1] ; Russo, Momtchilo ^[2]

Affiliation

^[1] Inst Butantan, Ctr Biotecnol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Imunol, Inst Ciencias Biomed, BR-05508000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med Ribeirao Preto, BR-05508000 Sao Paulo - Brazil

• Document type: Journal article
• Source: American Journal of Respiratory Cell and Molecular Biology; v. 43, n. 2, p. 243-252, AUG 2010.
• Web of Science Citations: 12

Abstract

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) has been shown to down-regulate experimental allergic asthma, a finding that reinforced the hygiene hypothesis. We have previously found that recombinant BCG (rBCG) strain that express the genetically detoxified Si subunit of pertussis toxin (rBCG-S1PT) exerts an adjuvant effect that enhances Th1 responses against BCG proteins. Here we investigated the effect of this rBCG-S1PT on the classical ovalbumin-induced mouse model of allergic lung disease. We found that rBCG-S1PT was more effective than wild-type BCG in preventing Th2-mediated allergic immune responses. The inhibition of allergic lung disease was not associated with increased concentration of suppressive cytokines or with an increased number of pulmonary regulatory T cells but was positively correlated with the increase in IFN-gamma-producing T cells and T-bet expression in the lung. In addition, an IL-12-dependent mechanism appeared to be important to the inhibition of lung allergic disease. The inhibition of allergic inflammation was found to be restricted to the lung because when allergen challenge was given by the intraperitoneal route, rBCG-S1PT administration failed to inhibit peritoneal allergic inflammation and type 2 cytokine production. Our work offers a nonclassical interpretation for the hygiene hypothesis indicating that attenuation of lung allergy by rBCG could be due to the enhancement of local lung Th1 immunity induced by rBCG-S1PT. Moreover, it highlights the possible use of rBCG strains as multipurpose immunomodulators by inducing specific immunity against microbial products while protecting against allergic asthma. (AU)

• FAPESP's process: 04/14297-6 - Activation/deactivation of macrophages and CD4+ T lymphocytes in experimental asthma
• Grantee: Momtchilo Russo
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 99/05202-1 - Development of recombinant vaccines against Streptococcus pneumoniae
• Grantee: Luciana Cezar de Cerqueira Leite
• Support Opportunities: Research Projects - Thematic Grants