UCLA

Leprosy is a human disease caused by the intracellular pathogen Mycobacterium leprae. By investigating leprosy, we discovered a novel pathway involving NOD2-mediated induction of interleukin-32 (IL-32) triggering the differentiation of M. leprae infected monocytes into CD1+ dendritic cells (DCs) with professional antigen presenting cell function. These IL-32-derived DCs were able to “cross-present” antigen, that is capture exogenous antigen via the endocytic pathway and then present processed peptides via MHC class I to CD8+ T cells. It was also discovered that key components of the NOD2->IL-32->CD1+ DC pathway were highly expressed only in lesions of leprosy patients with cell-mediated immunity. We hypothesized that cross-presentation of M. leprae antigens by IL-32-derived DCs resulted in the activation of MHC class I-restricted CD8+ T cells. To test our hypothesis, we established CD8+ T cell clones from leprosy patients to putatively secreted M. leprae antigens. IL-32-derived DCs were able to cross-present exogenous recombinant M. leprae protein as well as live M. leprae to the CD8+ T cell clones. We conclude that IL-32-induced cross-presentation may play a role in CD8+ T cell responses in leprosy.