Senior Research Immunologist
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.
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 target macrophages after interaction with normal and activated effector macrophages. J. Immunol. 172:7771-7779.
Scollard, D.M., L. B. Adams, T. P. Gillis, J. L. Krahenbuhl, R. W. Truman, and D. L. Williams. 2006. The continuing challenges of leprosy. Clin. Microbiol. Rev. 19: 338-381.
Hagge, D.A., V.T. Marks, N.A. Ray, M.A. Dietrich, M.T. Kearney, D.M. Scollard, J.L. Krahenbuhl, and L.B. Adams. 2007. Emergence of an effective adaptive cell mediated immune response to Mycobacterium leprae is not impaired in reactive oxygen intermediate-deficient mice. FEMS Immunol. Med. Microbiol. 51:92-101.
Peña, M.T, J.E. Adams, L.B. Adams, T.P. Gillis, D.L. Williams, J.S. Spencer, J.L. Krahenbuhl, and R.W. Truman. 2008. Expression and characterization of recombinant interferon gamma (IFN-γ) from the nine-banded armadillo (Dasypus novemcinctus) and its effect on Mycobacterium leprae-infected macrophages. Cytokine. 43:124-131.
Hagge, D.A., B.M. Saunders, G.J. Ebenezer, N.A. Ray, V.T. Marks, W.J. Britton, J.L. Krahenbuhl, and L.B. Adams. 2009. Lymphotoxin-a and TNF have essential but independent roles in the evolution of the granulomatous response in experimental leprosy. Am. J. Path. 174:1379-1389.