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An In Vitro Model for the Lepromatous Leprosy Granuloma: Fate of Mycobacterium leprae from Target Macrophages after Interaction with Normal and Activated Effector Macrophages¹

National Hansen’s Disease Programs, Laboratory Research Branch, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803

The lepromatous leprosy granuloma is a dynamic entity requiring a steady influx of macrophages (M) for its maintenance. We have developed an in vitro model to study the fate of Mycobacterium leprae in a LL lesion, with and without immunotherapeutic intervention. Target cells, consisting of granuloma M harvested from the footpads of M. leprae-infected athymic nu/nu mice, were cocultured with normal or IFN--activated (ACT) effector M. The bacilli were recovered and assessed for viability by radiorespirometry. M. leprae recovered from target M possessed high metabolic activity, indicating a viable state in this uncultivable organism. M. leprae recovered from target M incubated with normal effector M exhibited significantly higher metabolism. In contrast, bacilli recovered from target M cocultured with ACT effector M displayed a markedly decreased metabolic activity. Inhibition by ACT M required an E:T ratio of at least 5:1, a coculture incubation period of 3–5 days, and the production of reactive nitrogen intermediates, but not reactive oxygen intermediates. Neither IFN- nor TNF- were required during the cocultivation period. However, cell-to-cell contact between the target and effector M was necessary for augmentation of M. leprae metabolism by normal effector M as well as for inhibition of M. leprae by ACT effector M. Conventional fluorescence microscopy and confocal fluorescence microscopy revealed that the bacilli from the target M were acquired by the effector M. Thus, the state of M infiltrating the granuloma may markedly affect the viability of M. leprae residing in M in the lepromatous lesion.

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