National Hansen's Disease Program

Research Interests: Linda B. Adams

Leprosy, with its broad immunopathological spectrum, represents a fascinating example of a human immunoregulatory disease. One of our research objectives is to develop murine models representative of the various positions on this spectrum. To this end we are studying the disease which develops upon Mycobacterium leprae infection of genetically engineered knockout mouse strains that carry gene deletions considered important in cell mediated immunity. Where appropriate, we are further modifying the cell mediated immune response in these knockout mice by conditionally knocking-out additional gene functions or selectively restoring certain disrupted gene functions to determine if these modifications induce changes in the disease presented (i.e. downgrading, upgrading, or a reactional episode) which provide clues regarding the instability observed in the borderline area of the leprosy spectrum.

In addition, we are examining the cellular interactions involved in the immune response to M. leprae , which is focused on the establishment, composition and configuration of a complex, three-dimensional, multicellular lesion called a granuloma. We are developing in vitro models for leprosy granulomas using both mouse and human derived immune cells. The goals of these studies are to advance our basic knowledge of the host response in resistance or anergy to M. leprae and provide useful models for studying granuloma formation and function. Understanding the mechanisms of immunity in leprosy could lead to means for preventing or predicting reactions and for identifying the key components of cell mediated immunity that need to be stimulated with an effective vaccine.

Representative Publications

Adams , L.B. , C.K. Job, and J.L. Krahenbuhl. 2000. Role of nitric oxide synthase in resistance to Mycobacterium leprae in mice. Infect. Immun. 68: 5462-5465.

Adams , L.B. , D.M. Scollard, N.A. Ray, A.M. Cooper, A.A. Frank, I.M. Orme, and J.L. Krahenbuhl. 2002. The study of Mycobacterium leprae infection in IFN- ? gene disrupted mice as a model to explore the immunopathologic spectrum of leprosy. J. Infect. Dis. 185: S1-8.

Adams , L.B. and J.L. Krahenbuhl. 2003. Human leprosy, p. 207-244. In D.L. Boros (ed.), Granulomatous Infections and Inflammations. ASM Press, Washington , D.C.

Hagge, D.A., N.A. Ray, J.L. Krahenbuhl, and L.B. Adams. 2004. An in vitro model for the lepromatous leprosy granuloma. Fate of Mycobacterium leprae from infected target macrophages after interaction with normal and activated effector macrophages. J. Immunol. 172:7771-7779.

D.M. Scollard, L.B. Adams, T.P. Gillis, J.L. Krahenbuhl, R.W. Truman, & D.L. Williams. 2006. The continuing challenges of leprosy. Clin. Microbiol. Rev. 19: 338-381.