The Progression of Tuberculosis
Due to its extensive prevalence in the human population, Mycobacterium tuberculosis (Mtb) remains a serious health risk, especially to individuals living with HIV. Tuberculosis vaccine development programs are hampered by poor understanding of the immune mechanisms underpinning disease progression.
To better understand microbial fitness and replication, David G. Russell, Microbiology and Immunology, is working to identify and characterize the host phagocytes—one type of the body’s immune cells—that restrict bacterial growth (controllers) versus phagocytes that promote bacterial growth (permissive). The overall goal is to discern the basis of disease progression in human tuberculosis.
Russell and his group hypothesize that using Mtb reporter strains—genes that express fluorescent proteins under specific environmental conditions—provides a novel route to identifying the host phagocyte populations that best restrict or promote bacterial replication. To these ends, they are developing and validating Mtb reporter strains in mouse models and characterizing phagocyte populations in nonhuman primates infected with Mtb.
In collaboration with Henry Mwandumba (Malawi-Liverpool-Wellcome Trust Clinical Research Programme) and Alasdair Leslie (Phillip T. and Susan M. Ragon Institute), they are also determining the phenotypes of human phagocyte subsets by probing the cells ex vivo with the fluorescent Mtb reporter strains. Findings will advance understanding of how Mtb navigates the immune system and will potentially point to new therapeutic targets. NIH Award Number: 1R01AI134183-01