HIV and TB are endemic in many regions around the world but disproportionately affect low-income countries. HIV/TB co-infections significantly worsen disease outcome with TB being the leading cause of death in people living with HIV (PLWH). Currently, the only vaccine for TB is the BCG vaccine which is not protective against adult pulmonary TB and not recommended for PLWH. Antiretroviral therapy (ART) can suppress viral loads and improve the life span in PLWH but is ultimately unable to eliminate the virus. Therefore, better therapeutic options are needed to improve outcomes for both HIV and TB infections.
IL-17 is a proinflammatory cytokine characteristically produced by Th17 cells. Utilizing a humanized mouse model, we aimed to investigate the role of IL-17 and Th17 cells in HIV and TB. HIV infection preferentially depleted Th17 cells in the blood and tissues of humanized mice. In TB infection, significantly increased numbers of Th17 cells were observed at 2 weeks post infection (p.i) in the lungs of M.tb infected mice compared to control and 4 weeks p.i. IL-17 levels trended higher in the lungs at 4 weeks p.i compared to control and 2 weeks. IL-17 depletion in acute TB infection showed slight decrease in bacterial load in the lungs of the treated mice compared to the control. This could suggest a potential pathological role of IL-17 in TB infection where IL-17 promotes M.tb replication. When exogenous IL-17 was administered to the lungs prior to TB infection, significantly higher numbers of CD4+ and CD8+ T cells in the lungs of treated mice were seen compared to the control but this did not affect bacterial load. Our current experiment administers exogenous IL-17 to HIV infected mice to assess how it would affect disease progression. Further investigation is needed to explore how IL-17 affects HIV and TB disease pathogenesis. / Thesis / Master of Science (MSc) / HIV and TB are diseases that place a huge burden on healthcare systems globally. Co-infections with HIV and TB worsen a patient’s prognosis significantly. Currently, antiretroviral therapy is used to treat HIV which can control infection but cannot eliminate the virus. The current vaccine for TB, the BCG vaccine is not completely efficacious for adults with TB, highlighting the urgent need for better vaccines and treatments for HIV and TB. IL-17 is a signalling molecule that has many effects on the immune system. Using mouse models that mimic human immune responses, we aimed to assess how IL-17 is involved in HIV and TB infections and if it can be used to develop new therapeutics for HIV and TB.
We found adding IL-17 to TB infected mice led to increased immune cell recruitment suggesting a beneficial role of IL-17. Further investigation is needed to fully assess IL-17’s role in infectious diseases.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/30372 |
| Date | 11 1900 |
| Creators | Lee, Victoria |
| Contributors | Gillgrass, Amy, Medical Sciences |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
Page generated in 0.0037 seconds