Abstract

This is a proposal to examine the pathobiology of patients with tuberculoid and lepromatous leprosy. In particular, we will define the cellular mechanisms necessary to mount a cell mediated response to M. leprae and to uncover the defects which result in the extensive replication of M. leprae in cutaneous macrophages. For this purpose we will analyze cells obtained from peripheral blood and the dermal lesions by both morphologic and functional studies. Each step in the triggering of T cells, the production of lymphokines and the activation of mononuclear phagocytes to a microbicidal state will be examined. The possible suppressor qualities of T cells and monocytes and soluble factors derived from them will be studied with M. laprae, other purified antigens and lectins, T cell triggering will be monitored by their replication and secretion of IL-2 and Gamma-IFN. Possible defects at the local dermal lesion will be analyzed. The ability of patients to mount a delayed hypersensitivity reaction and mobilize the appropriate subsets of immune cells will be assessed. The capacity of dermal macrophages to ingest, incorporate into a phagolysosome and kill M. leprae in the presence or absence of exogenous Gamma-IFN will be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI022616-03
Application #
3444851
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1986-04-01
Project End
1989-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Rockefeller University
Department
Type
Graduate Schools
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Berrington, William Richard; Macdonald, Murdo; Khadge, Saraswoti et al. (2010) Common polymorphisms in the NOD2 gene region are associated with leprosy and its reactive states. J Infect Dis 201:1422-35
Sapkota, Bishwa R; Macdonald, Murdo; Berrington, William R et al. (2010) Association of TNF, MBL, and VDR polymorphisms with leprosy phenotypes. Hum Immunol 71:992-8
Bochud, P-Y; Sinsimer, D; Aderem, A et al. (2009) Polymorphisms in Toll-like receptor 4 (TLR4) are associated with protection against leprosy. Eur J Clin Microbiol Infect Dis 28:1055-65
Reich-Slotky, Ronit; Kabbash, Christina A; Della-Latta, Phyllis et al. (2009) Gemfibrozil inhibits Legionella pneumophila and Mycobacterium tuberculosis enoyl coenzyme A reductases and blocks intracellular growth of these bacteria in macrophages. J Bacteriol 191:5262-71
Bochud, Pierre-Yves; Hawn, Thomas R; Siddiqui, M Ruby et al. (2008) Toll-like receptor 2 (TLR2) polymorphisms are associated with reversal reaction in leprosy. J Infect Dis 197:253-61
Misch, Elizabeth A; Macdonald, Murdo; Ranjit, Chaman et al. (2008) Human TLR1 deficiency is associated with impaired mycobacterial signaling and protection from leprosy reversal reaction. PLoS Negl Trop Dis 2:e231
Murray, Rose Ann; Mansoor, Nazma; Harbacheuski, Ryhor et al. (2006) Bacillus Calmette Guerin vaccination of human newborns induces a specific, functional CD8+ T cell response. J Immunol 177:5647-51
Davids, Virginia; Hanekom, Willem A; Mansoor, Nazma et al. (2006) The effect of bacille Calmette-Guerin vaccine strain and route of administration on induced immune responses in vaccinated infants. J Infect Dis 193:531-6
Mendelson, Marc; Hanekom, Willem A; Ntutela, Siyabulela et al. (2006) Quantitative and functional differences between peripheral blood myeloid dendritic cells from patients with pleural and parenchymal lung tuberculosis. Clin Vaccine Immunol 13:1299-306
Freeman, Sherry; Post, Frank A; Bekker, Linda-Gail et al. (2006) Mycobacterium tuberculosis H37Ra and H37Rv differential growth and cytokine/chemokine induction in murine macrophages in vitro. J Interferon Cytokine Res 26:27-33

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