The Role of Inflammation in the Pathobiology of TB/HIV Co-infection

dc.creatorHuante, Matthew
dc.creator.orcid0000-0002-6604-9603 2017
dc.description.abstractMycobacterium tuberculosis (M.tb), the etiological agent of tuberculosis (TB), is the leading cause of death in people living with Human Immunodeficiency Virus (HIV). Treatment of co-infected persons is challenging due to the aggressive course of both individual diseases, and often is further complicated by drug interaction and malabsorption issues when combining antiretroviral treatment and TB chemotherapy. The molecular basis for pathogen synergy that leads to an aggressive course of TB in those with HIV-1 infection, however, is poorly defined. This is especially true at earlier stages of disease prior to the immune suppression that occurs due to CD4+T cell loss. Using our newly developed humanized mouse model of TB/HIV co-infection, we find that initial acute co-infection in the lung is characterized by excessive inflammation. We observed greater pathology, inflammatory influx, and increased pro-inflammatory cytokines (e.g. IL-1, TNF) in co-infected HuMouse lung. Using primary human monocyte-derived macrophages (MDM) and an in vitro co-infection system, we further observed greater cell death and increased expression of pro-inflammatory cytokines in co-infected MDMs compared to mono-infection with either HIV-1 or M.tb. Analysis of cellular lysates demonstrates that increased caspase-1 activation due to HIV, and increased production of pro-IL-1 due to M.tb, may promote the overall increase in active IL-1 and cell death observed in co-infected MDMs. These studies suggest that convergence of pathogen pattern recognition signaling in macrophages may promote an exacerbated pro-inflammatory response and tissue damage in the M.tb/HIV co-infected lung.
dc.subjectTuberculosis, HIV
dc.titleThe Role of Inflammation in the Pathobiology of TB/HIV Co-infection
dc.type.materialtext and Immunology University of Texas Medical Branch at Galveston and Immunology (Doctoral)


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