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Infection and Immunity, November 2006, p. 6264-6271, Vol. 74, No. 11
0019-9567/06/$08.00+0     doi:10.1128/IAI.00878-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Immunostimulatory Activity of Recombinant Mycobacterium bovis BCG That Secretes Major Membrane Protein II of Mycobacterium leprae

Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aobacho, Higashimurayama, Tokyo 189-0002, Japan

Received 2 June 2006/ Returned for modification 10 July 2006/ Accepted 4 August 2006

We previously demonstrated that major membrane protein II (MMP-II) is one of the immunodominant antigens (Ags) of Mycobacterium leprae capable of activating T cells through Toll-like receptor 2. Based on the observation that Mycobacterium bovis BCG secreting a 30-kDa protein offered better protection against tuberculosis, we constructed a recombinant BCG strain (BCG-SM) that secretes MMP-II to improve the potency of BCG against leprosy. The secreted MMP-II protein from BCG-SM stimulated monocyte-derived dendritic cells (DC) to produce interleukin-12. DC infected with BCG-SM expressed MMP-II on their surfaces, and MMP-II expression was suppressed by the pretreatment of DC with chloroquine. These results indicated that secreted MMP-II was processed by DC for higher expression levels on their surfaces. In addition, BCG-SM phenotypically activated DC and induced higher expression levels of major histocompatibility complex, CD86, and CD83 Ags on DC than did vector control BCG (BCG-pMV). The DC infected with BCG-SM more efficiently stimulated naïve and memory CD4⁺ T cells and memory CD8⁺ T cells to produce gamma interferon than did those infected with BCG-pMV. However, naïve CD8⁺ T cells were significantly activated only when they were stimulated with BCG-SM-infected DC. When CD8⁺ T cells were cocultured with BCG-SM-infected DC, the proportion of perforin-producing T cells was significantly higher than that in cells cocultured with BCG-pMV-infected DC. Moreover, MMP-II-specific memory T cells were more efficiently produced in mice inoculated with BCG-SM than in mice inoculated with BCG-pMV. Taken together, these results indicate that BCG capable of secreting the immunodominant Ag is more potent in the stimulation of T cells.

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