Abstract

This study is proposed to investigate the mechanisms of responsiveness or unresponsiveness in leprosy. The disease forms a spectrum with tuberculoid patients having strong cell-mediated immune (CMI) responses to Mycobacterium leprae while lepromatous patients are unresponsive perhaps due to antigen specific suppressor cells. Why both patient contacts and tuberculoid patients have positive CMI to M. leprae but only tuberculoid patients manifest clinical disease is unknown. We plan to obtain T4 and T8 lymphocyte clones from tuberculoid and lepromatous skin lesions and lepromin skin tests of patient contacts. These clones will be tested for reactivity to M. leprae specific cloned proteins and glycolipid. Our preliminary data demonstrates the feasibility of the proposed methods as well as demonstrating lepromin induced suppressor T lymphocytes from lepromatous lesions. We plan to investigate further the mechanism of action of suppressor lymphocytes in lepromatous leprosy. These studies will improve our understanding of leprosy and aid in developing skin test reagents and vaccines.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI022553-02
Application #
3444839
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1986-04-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90033

  Publications

Chung, Andrew W; Sieling, Peter A; Schenk, Mirjam et al. (2013) Galectin-3 regulates the innate immune response of human monocytes. J Infect Dis 207:947-56
Schenk, Mirjam; Krutzik, Stephan R; Sieling, Peter A et al. (2012) NOD2 triggers an interleukin-32-dependent human dendritic cell program in leprosy. Nat Med 18:555-63
Torrelles, Jordi B; Sieling, Peter A; Zhang, Nannan et al. (2012) Isolation of a distinct Mycobacterium tuberculosis mannose-capped lipoarabinomannan isoform responsible for recognition by CD1b-restricted T cells. Glycobiology 22:1118-27
Liu, Philip T; Wheelwright, Matthew; Teles, Rosane et al. (2012) MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy. Nat Med 18:267-73
Fabri, Mario; Stenger, Steffen; Shin, Dong-Min et al. (2011) Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci Transl Med 3:104ra102
Fabri, Mario; Realegeno, Susan E; Jo, Eun-Kyeong et al. (2011) Role of autophagy in the host response to microbial infection and potential for therapy. Curr Opin Immunol 23:65-70
Modlin, Robert L (2010) The innate immune response in leprosy. Curr Opin Immunol 22:48-54
Lee, Delphine J; Li, Huiying; Ochoa, Maria T et al. (2010) Integrated pathways for neutrophil recruitment and inflammation in leprosy. J Infect Dis 201:558-69
Edfeldt, Kristina; Liu, Philip T; Chun, Rene et al. (2010) T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism. Proc Natl Acad Sci U S A 107:22593-8
Teles, Rosane M B; Krutzik, Stephan R; Ochoa, Maria T et al. (2010) Interleukin-4 regulates the expression of CD209 and subsequent uptake of Mycobacterium leprae by Schwann cells in human leprosy. Infect Immun 78:4634-43

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