A complex component modulating immune-deficient cells in leprosy patients leading to loss of viability of Mycobacterium leprae--a possible vaccine.

Macrophages from peripheral blood of leprosy patients, both multi-bacillary and paucibacillary are unable to kill phagocytosed Mycobacterium leprae due to their inability to produce superoxide (O2-) and hydroxyl radicals (OH.). The macrophages from healthy individuals are able to kill M. leprae along with release of O2- and OH. radicals. The deficiency in the macrophages of both types of leprosy patients is removed by activation of these cells when exposed to a culture supernatant obtained after stimulation of peripheral blood mononuclear cells from the same patients with delipidified cell components of M. leprae which are most likely cell wall proteins. The activation of macrophages also leads to recognition of whole live M. leprae as an antigen by cells from lepromatous patients. This activation of the phagocytes by delipidified cell components is blocked by cyclosporin A, indicating the possible role of several steps involved in immune activation of cells. The observations thus indicate the significant ability of delipidified cell components to eliminate the deficiencies in the macrophages from leprosy patients and restore them to behave like the cells from healthy individuals. Considering all these, it is suggested that delipidified cell components could be potential modulators, and are probably capable of functioning as a vaccine for leprosy.

Reactive oxygen intermediates inactivate Mycobacterium leprae in the phagocytes from human peripheral blood.

Reactive oxygen intermediates such as hydrogen peroxide, superoxide, and hydroxyl radicals are important microbicidal components, and they could also play a role in an infection with Mycobacterium leprae. A comparative study of the level of hydrogen peroxide and superoxide produced by peripheral blood phagocytes from normal healthy individuals and lepromatous leprosy patients showed a deficiency in superoxide production in the patients. In the phagocytes from normal healthy individuals, there was good release of superoxide ions, and this mediated the killing of M. leprae. The lack of superoxide production allowed the viability of M. leprae inside the macrophages from leprosy patients. This deficiency could be rectified by the use of an immunomodulator, the delipidified cell wall of M. leprae. This modulation resulted in the ability of the patients' phagocytes to respond to M. leprae, to produce reactive oxygen intermediates such as superoxide, and also to kill the bacteria. These observations indicate that delipidified cell wall could have significant potential to positively modulate the immune-deficient cells of leprosy patients.

Hydrolytic enzymes in macrophages from leprosy patients in presence of Mycobacterium leprae.

Presence of Mycobacterium leprae in association with in vitro cultured macrophages, from bacillary negative long term treated lepromatous leprosy patients, induces reduced level of protein and lowering of hydrolytic enzymes like p-glucuronidase, Lysozyme and Lactic dehydrogenase. Alkaline phosphatase, on the other hand is increased. In the macrophages from normal healthy individuals or tuberculoid leprosy patients, presence of M.leprae increases both protein and levels of all the above enzymes. This observation shows that macrophages from lepromatous leprosy patients are unable to manifest in presence of M. leprae, the key enzymes involved in degradation of complex biological entities phagocytosed by the cells.