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Effect of Mycobacterium tuberculosis on HIV Replication

Effect of Mycobacterium tuberculosis on HIV Replication. Presented by Celeste Nadal. Based on an article by D Goletti, D Weissman, R Jackson, N Graham, D Vlahov, R Klein, S Munsiff, L Ortona, R Cauda and AS Fauci The Journal of Immunology 1996 157: 1271-1278. History. 1950’s-1980’s

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Effect of Mycobacterium tuberculosis on HIV Replication

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  1. Effect of Mycobacterium tuberculosis on HIV Replication Presented by Celeste Nadal Based on an article by D Goletti, D Weissman, R Jackson, N Graham, D Vlahov, R Klein, S Munsiff, L Ortona, R Cauda and AS Fauci The Journal of Immunology 1996 157: 1271-1278

  2. History • 1950’s-1980’s • Decline in Mycobacterium tuberculosis (MTB) disease cases • 1980s-present • HIV identified • AIDS cases increases MTB cases increases • Combined AIDS and MTB disease (MTBD) leads to decreased life expectancy

  3. Rationale • Determine if MTB disease increases HIV replication in vivo • Determine if MTB disease increases HIV replication in vitro

  4. Background • PBMCs- Peripheral Blood Mononuclear Cells • CD4+ T-cells, CD8+ T-cells, Monocytes and macrophages • Two types of T-cells • CD4+ T-cells (Helper T-cells) • CD8+ T-cells (Cytotoxic T-cells) • LNMCs- Lymph Node Mononuclear Cells • Cytokines- proteins excreted in response to antigen • PPD- Purified Protein Derivative • Creates an immune response • Test for MTB exposure

  5. Methods • Clinical Specimens- • Blood samples obtained from HIV+ individuals (CD4+ T-cell count 13 to 1150 cells/microliter) • PBMCs were isolated from blood • LBMCs were isolated by excision lymph node biopsies • Branched DNA (bDNA) analysis • Quantifies HIV-1 RNA plasma levels

  6. Methods • Reverse Transcriptase (RT) Assay • Quantifies RT activity • 3H-thymidine Incorporation • Measures cell proliferation Cellular Activation • Determined by • Increased CD4+/CD25+ T-cells • IL-2 (a cytokine) secretion

  7. HIV replication increases during MTBD in vivo

  8. CD8+ T-cells inhibit MTB/PPD induced HIV replication in HIV+, PPD+ PBMCs

  9. CD8+ T-cells has no effect on MTB/PPD induced HIV replication in HIV+, PPD- PBMCs CD8+ T-cell depleted PBMCs

  10. CD8+ T-cells inhibit MTB/PPD induced HIV replication in HIV+, PPD+ LNMCs

  11. MTB/PPD induced HIV replication leads to cellular activation and proliferation HIV+, PPD+ CD8+ T-cell depleted PBMCs Day 6

  12. MTB/PPD induced HIV replication leads to cell death

  13. Effect on MTB/PPD induced HIV replication in acutely HIV infected PBMCs

  14. Conclusion • MTB increases HIV replication in the in vivo and in vitro model • Mechanism- Antigen specific CD4+ T-cell activation • Strong correlation between increased HIV replication upon secondary exposure

  15. Implications • Anti-MTB treatment is necessary • Adherence • Multi-drug treatment • Vaccines are not a good idea • Other infections probably cause similar effect

  16. Questions????

  17. Results

  18. Results

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