The javascript used on this site for creative design effects is not supported by your browser. Please note that this will not affect access to the content on this web site.
Skip Navigation
H H S Department of Health and Human Services
U.S. Department of Health and Human Services
Health Resources and Services Administration

A-Z Index  |  Questions? 

  • Print this
  • Email this

Hansen's Disease Research

Dr. Linda B. Adams


 

Head, Immunology Research Section
Ph.D. 1987
Louisiana State University
Baton Rouge, LA
ladams@hrsa.gov

Leprosy is classified as a clinical, histopathological, and immunological spectrum, ranging from tuberculoid disease with a high level of cell mediated immunity (CMI) to complete anergy in lepromatous disease. One of our research objectives is to develop murine models representative of the various positions on this spectrum. To accomplish this we are studying the disease which develops upon Mycobacterium leprae infection of genetically engineered mouse strains, including knockout strains that carry gene deletions considered important in CMI. Where appropriate, we are further modifying the CMI response in these knockout mice by conditionally knocking-out additional gene functions or selectively restoring certain disrupted gene functions via cytokine therapy to determine if these modifications induce changes in the disease presented. These studies could provide clues regarding the instability observed in the borderline areas of the leprosy spectrum and could lead to a means for preventing or predicting reactions.

We are also examining the cellular interactions involved in the immune response to M. leprae, which is focused on the establishment, composition and configuration of the granuloma. We are characterizing the granulomatous response upon foot pad or intra-nerve infection, as well as developing in vitro granuloma models using mouse derived immune cells. Understanding the basic mechanisms of immunity in leprosy and identifying the key components of CMI could benefit development of effective vaccines and therapeutics.

An important consideration in evaluating the immune response in leprosy is assessing killing of the pathogen. Determining the viability of M. leprae is extremely difficult, however, because of the inability to culture the organism in vitro and its slow growth rate. Using the mouse foot pad model, we are developing molecular based assays for assessing M. leprae viability directly in tissues. Current research efforts are examining the feasibility of translating these assays to clinical specimens.

Representative Publications

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.

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-α and TNF have essential but independent roles in the evolution of the granulomatous response in experimental leprosy. Am. J. Path. 174:1379-1389.

Adams, L.B., M.T. Pena, R. Sharma, D.A. Hagge, E. Schurr, and R.W. Truman. 2012. Insights from animal models on the immunogenetics of leprosy – A Review. Mem. Inst. Oswaldo Cruz. 107 (Suppl. 1): 197-208.

Davis, G.L., N.A. Ray, R. Lahiri, T.P. Gillis, J.L. Krahenbuhl, D.L. Williams, and L.B. Adams. 2013. Molecular assays for determining Mycobacterium leprae viability in tissues of experimentally infected mice. PLoS Negl. Trop. Dis. 7(8): e2404. doi:10.1371/journal.pntd.0002404.

Hagge, D.A., D.M. Scollard, N.A. Ray, V.T. Marks, A.T. Deming, J.S. Spencer, and L.B. Adams. 2014. IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy. PLoS Negl. Trop. Dis. 8(9): e3149. doi:10.1371/journal.pntd.0003149.

For more comprehensive list of Dr. Adams’ publications