title: Enhancement of Th1 lung immunity induced by recombinant Mycobacterium bovis Bacillus Calmette-Guerin attenuates airway allergic disease.
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 S1 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.
authors.affiliation: Centro de Biotecnologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Christ
authors.forename: Dúnia
authors.initials: D
authors.lastname: Rodriguez
authors.forename: Juliana
authors.initials: J
authors.lastname: Bortolatto
authors.forename: Erica
authors.initials: E
authors.lastname: Borducchi
authors.forename: Alexandre
authors.initials: A
authors.lastname: Keller
authors.forename: Daniel
authors.initials: D
authors.lastname: Mucida
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
authors.forename: Luciana C C
authors.initials: LC
authors.lastname: Leite
authors.forename: Momtchilo
authors.initials: M
authors.lastname: Russo
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000382:microbiology; D005260:Female; D006967:Hypersensitivity / Q000382:microbiology*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology* / Q000378:metabolism*; D010047:Ovalbumin / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000382:microbiology*; D018418:Th2 Cells / Q000382:microbiology
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma; D010047:Ovalbumin