1 / 18

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

emily
Télécharger la présentation

Effect of Mycobacterium tuberculosis on HIV Replication

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related