Fellowship

Immunometabolic profiling of immune cells in subclinical TB patients

Wadzanai Majeese’s research is focused on generating three dimensional (3D) spheroids (alginate microspheres) incorporating virulent Mycobacterium tuberculosis (Mtb) H37Rv and peripheral blood mononuclear cells (PBMCs). The microspheres form a granuloma similar to occurrence in human infection. Mtb is allowed to grow within the matrix and the aim is to identify a metabolic profile of immune cells (NK cells, T cells, monocytes, dendritic cells and NKT cells) during infection and compare with mycobacterium infection from the vaccine strain (M.bovis BCG) that is known to be controlled by the immune system. The expression of different metabolic check point markers, glucose transporters, oxidative phosphorylation complexes, and regulators will then be measured using flow cytometry. The metabolic profiling of the different immune cells in a Mtb infected 3D spheroid system is a preliminary study towards the metabolic profiling of immune cells in subclinical TB patients. With the study, Manjeese hopes to identify distinct metabolic trends in some immune cells without delays arising from confounding factors (gender, age, HIV, diabetes, etc) in a cohort. This should narrow down the immune cell population of interest. Manjeese’s preliminary study will give direction of the larger and main clinical study.

SANTHE is an Africa Health Research Institute (AHRI) flagship programme funded by the Science for Africa Foundation through the DELTAS Africa programme; the Bill & Melinda Gates Foundation; Gilead Sciences Inc.; and the Ragon Institute of Mass General, MIT, and Harvard.