We report on the characteristics of cells in the cutaneous lesions and blood of 21 patients with lepromatous, tuberculoid, and intermediate forms of leprosy. A large proportion of the infiltrates in lepromatous lesions consist of macrophages heavily parasitized with Mycobacterium leprae. The T cells in the lesions are devoid of OKT4/Leu 3a-positive ("helper") cells and consist almost exclusively of OKT8/Leu 2a-positive ("suppressor") populations. In contrast, the tuberculoid infiltrates contain well-organized epithelioid and giant-cell granulomas and only remnants of bacilli, and the predominant T cell is from the OKT4/Leu 3a-positive subset. In both tuberculoid and lepromatous infiltrates, T cells and macrophages expressed HLA-DR antigen. No marked alteration in the distribution of blood T-cell phenotypes was noted. We conclude that there is a marked difference between T-cell subsets in lepromatous and tuberculoid infiltrates, which may influence the microbicidal activity of macrophages in the lesions.

The initial interaction between a microbial pathogen and the host immune response influences the outcome of the battle between the host and the foreign invader. Leprosy, caused by the obligate intracellular pathogen Mycobacterium leprae, provides a model to study relevant human immune responses. Previous studies have adopted a targeted approach to investigate host response to M. leprae infection, focusing on the induction of specific molecules and pathways. By measuring the host transcriptome triggered by M. leprae infection of human macrophages, we were able to detect a host gene signature 24-48 hours after infection characterized by specific innate immune pathways involving the cell fate mechanisms autophagy and apoptosis. The top upstream regulator in the M. leprae-induced gene signature was NUPR1, which is found in the M. leprae-induced cell fate pathways. The induction of NUPR1 by M. leprae was dependent on the production of the type I interferon (IFN), IFN-β. Furthermore, NUPR1 mRNA and protein were upregulated in the skin lesions from patients with the multibacillary form of leprosy. Together, these data indicate that M. leprae induces a cell fate program which includes NUPR1 as part of the host response in the progressive form of leprosy.