Mechanisms of Immunological Unresponsiveness in the Spectra of Leprosy and Leishmaniasis

Abstract

Leprosy and cutaneous leishmaniasis share a number of important characteristics^1,2. They are both chronic granulomatous diseases; both affect the skin and both present a spectrum of clinical manifestations. In the case of leprosy, there is a remarkable correlation between the clinical and histopathological spectrum, and cell-mediated immune responsiveness to antigens of M. leprae. At the tuberculoid pole, patients have few lesions which contain rare organisms and are able to mount strong T-cell-mediated immune responses to M. leprae antigens in vitro and in vivo. In contrast, at the lepromatous end of the spectrum, patients have disseminated skin lesions containing large numbers of acid-fast bacilli and are selectively unresponsive to antigens of M. leprae. In American cutaneous leishmaniasis, the spectrum is somewhat less well defined, more variable clinically and less predictable at the histopathologic level. The disease ranges from a single defined lesion containing few amastigotes in localized cutaneous leishmaniasis (LCL) to diffuse cutaneous leishmaniasis (DCL) which, like lepromatous leprosy, is characterized by disseminated granulomata containing macrophages laden with amastigotes and immune unresponsiveness to leishmanial antigens. There are other clinical forms of cutaneous leishmaniasis including the highly destructive mucocutaneous (espundia) form, and a verrucous form, the pathogenesis of which are not entirely predictable from histopathology and molecular immunological data. In addition, in different parts of the world systemic forms of visceral leishmaniasis (kala-azar) occur in Asia, and a mild local form, Oriental Sore, exists in the Middle East primarily. Antibody levels appear to be elevated in both lepromatous leprosy and in diffuse cutaneous leishmaniasis, indicating that antibodies are unlikely to play a major role in protection.