Attenuation of allergic airway inflammation and associated pulmonary functions by mycobacterial antigens is independent of IgE in a mouse model of asthma

Abstract

Since the observation that Bacillus Calmette–Guérin (BCG) vaccination in children correlates with a decreased prevalence of asthma, several investigators have been attempting to reproduce this effect experimentally in mouse models of asthma. While these reports have agreed in some areas, uncertainty has remained as to the effect of BCG on IgE and asthmatic response in general. Furthermore, the effect of mycobacterial antigens on the early allergic response and the release of bronchoconstrictory mediators have not been examined. In the present study, we have aimed to more completely describe the effect of BCG and Mycobacterium vaccae on early and late allergic responses (EAR and LAR, respectively), airway hyperresponsiveness (AHR) and broncho-constrictory mediators in the mouse model of allergic airway inflammation. Using BALB/c mice sensitized to ovalbumin (OVA) and treated twice with either BCG or M. vaccae (1 × 105 CFU, intranasally), we investigated airway resistance of both the EAR and LAR, AHR to methacholine, serum total and antigen-specific IgE, cysteinyl leukotrienes in bronchoalveolar lavage (BAL) fluid (10 min following challenge), a complete cell differential of the BAL (24 h post-challenge), BAL and serum cytokines and lung histology. Neither BCG nor M. vaccae were able to attenuate the EAR, yet both were able to abrogate the parameters used to evaluate the LAR. Interestingly, in neither case were serum or OVA-specific IgE levels reduced after treatment with mycobacterial antigens and type 1/type 2 T cell cytokine skewing, based on cytokine levels in BAL and serum, was incomplete. These results have led us to conclude that the mycobacterial antigens elicit potential anti-asthmatic effects independent of changes in IgE levels. We speculate that mycobacteria likely directly or indirectly suppress eosinophil effector function via attenuation of type 2 T cell-mediated immune responses.