Subcutaneous Vaccination of Mycobacterium bovis Bacillus Calmette-Guérin Attenuates Allergic Inflammation in a Murine Model of Asthma

Abstract

Background: The increase in the incidence of allergic disorders especially in developed countries may be explained by the hygiene hypothesis. A novel therapeutic approach that causes a Th1-dominant response under conditions of Th2-skewed immunity has been investigated. Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is a widely used anti-tuberculosis vaccine that strongly induces a Th1-predominant immune response. A potential role for BCG in the treatment of allergic diseases has been reported. In the present study, we investigated whether subcutaneous inoculation with a low dose (1 × 105) of BCG vaccine can attenuate allergic inflammation of the airway in a murine model of asthma. Methods: Female BALB/c mice were vaccinated on day 0 with a subcutaneous. injection of 1 × 105 CFU of BCG, and sensitized to ovalbumin (OVA, i.p., with alum) on day 7 and 14, respectively. After a 2-week interval, they were exposed to aerosolized OVA (1%). In another experiment, BCG-sensitized splenic CD4+ T cells were adoptively transferred before sensitization. Results: We found that BCG-vaccinated mice had fewer eosinophils in BALF and less severe allergic inflammation. The expression of IL-4 as well as Eotaxin and TARC was down-regulated in the vaccinated mice, while that of both IL-12 and IFN-γ was up-regulated. Moreover, the transfer of splenic CD4+ T cells from vaccinated mice into naive mice before OVA-sensitization prevented the development of allergic inflammation. These splenic CD4+ T cells produced much IFN-γ. Conclusions: The subcutaneous administration of (low-dose) BCG vaccine suppressed allergic inflammation via Th1-skewed immunity and might have clinical applications in immunotherapy for asthma.

Keywords

• asthma
• CD4+ T cell
• chemokine
• Mycobacterium bovis
• Th1/Th2