The objective of this pilot project is to continue the characterization of the tuberculosis model in rhesus monkeys. We previously found that high dose inoculation (six million bacteria) of Mycobacterium tuberculosis H37Rv and Erdman strains produced lethal lung disease within five to ten weeks. Monkeys developed clinical signs of dyspnea, coughing, anorexia, and weight loss 4-6 weeks after inoculation. Skin testing with Old tuberculin became mildly positive after 5 weeks while PPD skin tests remained negative. Animals developed extensive necrotizing granulomatous lesions in the inoculated half of the lung with spread to the contralateral lung and bronchial lymph node in animals with H37Rv, and to the liver and kidney in animals with the Erdman strain. Animals vaccinated with culture filtrate from H37Rv and challenged with two million bacteria developed the same clinical disease as unvaccinated controls. However, low dosage inoculation of a pair of animals with each strain (<300 Erdma n, <30 H37Rv) failed to produce clinical disease within 18 weeks. Lesions in three of four animals were confined to the bronchial lymph node. To confirm this finding, four more animals per strain have been inoculated with low dosages of bacteria. All animals have strongly positive skin tests but remain clinically normal four weeks after inoculation. Characterization of this model by culture, blastogenesis, flow cytometry, and cytokine detection continues. Results contradict old literature and indicate that tuberculosis in rhesus monkeys may present as a chronic disease based on the dose of the inoculum. This suggests that future studies using low dose inoculation will be feasible in SIV-infected monkeys to study tuberculosis as an opportunistic infection. FUNDING Venture Research PUBLICATIONS Scollard DM, Didier PJ, Dietrich MA, Bohm Jr RP. Selective increases in CD45RO(+) CD38(+) T cells in 1? and 2? responses to BCG in rhesus macaques. [Abstract]. Proceedings of the 9th International Immunology Congress, San Francisco, CA, July 23-29, 1995. Scollard DL, Didier PJ, Bohm Jr RP. A method to assess changes in rhesus lymphatic T cells in vivo during local immune responses. [Abstract]. Second Annual Molecular Biology and Biotechnology Conference, Baton Rouge, LA, February 9-10, 1996. Didier PJ, Blanchard JL, Gormus BJ. Pulmonary tuberculosis in normal rhesus monkeys infected with Mycobacterium tuberculosis H37Rv. [Abstract #159]. Amer Soc Trop Med Hygiene, 57(3):156, 1997. Didier PJ, Blanchard JL. Chronic tuberculosis produced by low dosage of M. tuberculosis (Erdman) in rhesus monkeys. [Abstract #734]. Amer Soc Trop Med Hygiene 59(3):361, 1998.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-41
Application #
6591710
Study Section
Project Start
2002-05-01
Project End
2003-04-30
Budget Start
Budget End
Support Year
41
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Tulane University
Department
Type
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Mahalingam, Ravi; Kaufer, Benedikt B; Ouwendijk, Werner J D et al. (2018) Attenuation of Simian Varicella Virus Infection by Enhanced Green Fluorescent Protein in Rhesus Macaques. J Virol 92:
Kumar, Vinay; Mansfield, Joshua; Fan, Rong et al. (2018) miR-130a and miR-212 Disrupt the Intestinal Epithelial Barrier through Modulation of PPAR? and Occludin Expression in Chronic Simian Immunodeficiency Virus-Infected Rhesus Macaques. J Immunol 200:2677-2689
Parthasarathy, Geetha; Philipp, Mario T (2018) Intracellular TLR7 is activated in human oligodendrocytes in response to Borrelia burgdorferi exposure. Neurosci Lett 671:38-42
McNamara, Ryan P; Costantini, Lindsey M; Myers, T Alix et al. (2018) Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses. MBio 9:
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Yi, Fei; Guo, Jia; Dabbagh, Deemah et al. (2017) Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol 91:
Jorgensen, Matthew J; Lambert, Kelsey R; Breaux, Sarah D et al. (2017) Pair housing of Vervets/African Green Monkeys for biomedical research. Am J Primatol 79:1-10
Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S et al. (2017) Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system. J Neuroinflammation 14:28
Parthasarathy, Geetha; Philipp, Mario T (2017) Receptor tyrosine kinases play a significant role in human oligodendrocyte inflammation and cell death associated with the Lyme disease bacterium Borrelia burgdorferi. J Neuroinflammation 14:110

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