Chapter 8 : Human Leprosy

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In humans, leprosy is fascinating for its great variability in the clinical course of the disease. Paucibacillary (PB) disease is mildest form of leprosy is classified as indeterminate disease and requires an experienced leprologist to even make the diagnosis, as bacilli are rarely seen. Identification of the various cellular components and their subsets in the leprosy lesion has greatly advanced our understanding of the pathogenesis of leprosy. In marked contrast, lepromatous leprosy (LL) lesions produced the TH2 cytokine mRNA for IL-4, and IL-10 was more prominent in LL than TT lesions The polar nature of the type of leprosy lesions chosen for a study by Modlin's group allowed evaluation of other local cytokines produced and demonstrated proinflammatory TNFα, IL-1B, IL-6, and IL-12 in the TT lesions, while anti-inflammatory IL-10 and IL-4 were found in LL. Preliminary studies failed to show a deleterious effect of granulysin for in an axenic system, but this work is being continued. The granulomas formed in wild-type mice in response to infection consisted of only small, focal collections of mononuclear cells; in contrast, the granulomas formed in iNOS KO mice contained large, dense, organized collections of epithelioid cells and lymphocytes which infiltrated the perineurium and destroyed muscle bundles. The cellular infiltrate, however, consisted of epithelioid Mø and scattered lymphocytes that were not assembled into organized granulomas. The opportunity remains for researchers to investigate immunoregulation in a fascinating, human, nonfatal infectious disease.

Citation: Adams L, Krahenbuhl J. 2003. Human Leprosy, p 207-244. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch8
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Figure 1

The immunopathological spectrum of leprosy. Upon exposure to most persons will not develop disease. Susceptible individuals may develop an indeterminate lesion, which may spontaneously heal or progress into the leprosy spectrum. The Ridley-Jopling classification combines clinical, immunological, and histopathological evidence and recognizes five forms of leprosy: tuberculoid (TT), borderline tuberculoid (BT), mid-borderline (BB), borderline lepromatous (BL), and lepromatous (LL) leprosy. The WHO classification is designed to fit two distinct multidrug therapy regimens and comprises two broad categories: paucibacillary (PB) disease, which includes TT and BT, and multibacillary (MB) disease, which includes BB, BL, and LL. Toward the PB end of the spectrum, the lesions display characteristics of well-developed CMI and possess few acid-fast bacilli (AFB), features of a TH1-type immune response. Toward the MB end of the spectrum, the immune response exhibits a TH2-type profile with a poorly developed CMI and numerous AFB. The borderline area of the spectrum is highly unstable and represents poorly understood immunoregulatory responses; BT and BB patients are prone to disfiguring reversal reactions, while BL (and LL) patients are subject to painful ENL reactions.

Citation: Adams L, Krahenbuhl J. 2003. Human Leprosy, p 207-244. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch8
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Figure 2

Murine models for leprosy. Upon infection with immunocompetent mice such as the C57BL/6 strain develop only mild lesions and allow limited growth of the bacilli, properties similar to the indeterminate form of leprosy. Certain immunodeficient strains, however, exhibit growth, histological, and immunological characteristics along the leprosy spectrum. iNOS KO mice develop features of BT disease, while GKO mice show characteristics of BB disease. Athymic nude mice display an LL leprosy-type profile. Additional study of these and other KO models may allow dissection of immunoregulation in leprosy and the mechanisms underlying reactional episodes.

Citation: Adams L, Krahenbuhl J. 2003. Human Leprosy, p 207-244. In Boros D (ed), Granulomatous Infections and Inflammations. ASM Press, Washington, DC. doi: 10.1128/9781555817879.ch8
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