Thesis Type:Undergraduate Senior Thesis
Abstract:The convergence of the Human Immunodeficiency Virus-1 (HIV) and Mycobacterium tuberculosis (Mtb) pandemics affects 1.1 million people worldwide. The synergistic interplay between these two pathogens may explain the enhanced risk of TB in HIV infection and the increased progression of HIV pathogenesis in the co-presence of Mtb infection. However, the molecular pathogenesis of coinfection that increasingly impairs immune function has yet to be fully elucidated. Most studies have focused on HIV-mediated depletion of CD4+ T cells as the major mechanism that drives bidirectional effects.In contrast, this thesis evaluates possible mechanisms of how HIV and Mtb may cooperate to modulate the innate immune system, specifically alveolar macrophages. Macrophages are one of the first cells infected by Mtb or HIV, and infected macrophages contribute significantly to the pathogenesis of each infection. The hypotheses assessed here thus focus on how coinfected macrophages contribute to the exacerbated symptoms and mortality rate in HIV/Mtb coinfected individuals. The risk for tuberculosis (TB) develops early on in HIV infection at relatively normal CD4+ T cell counts but increases as immunosuppression worsens. By assessing the available literature on coinfection, I argue that the pathogens impair macrophage functions, including interactions with CD4+ T cells, which ultimately contributes to the enhanced morbidity and mortality. Dysregulation of macrophage functions contribute to the synergistic effects of coinfection and merits further study. Future research should focus on using models like lung organoids, animal models, and new imaging technologies to clarify the role of innate immunity in coinfection. Developing molecular epidemiological tools will also be critical to understanding transmission of Mtb in HIV+ individuals. These techniques will help elucidate host-pathogen dynamics and innate immunity in response to a broad range of infectious pathogens. Furthermore, as the risk of TB increases early in HIV infection, prevention and early treatment are critical. A comparative case study of coinfected populations in South Africa and the U.S. is used to contrast policies for expanding treatment and prevention coverage in areas of high or low TB/HIV burden respectively.