Role of mitochondrial oxidative stress on lymphocyte homeostasis in patients diagnosed with extra-pulmonary tuberculosis

Extra-pulmonary tuberculosis is often an underrated illness. Recent clinical studies have pointed out that lymphocyte homeostasis is dramatically disturbed as revealed through a series of signs and symptoms. Lymphocytes, the known effector cells of our immune system, play an important role in providing immunologic resistance against Mycobacterium infection. It is important to have quantitative insights into the lifespan of these cells; therefore, we aimed to study the precise effect of gastrointestinal tuberculosis infection on peripheral blood lymphocyte subpopulations and function. Our results indicated that gastrointestinal tuberculosis could increase mitochondrial oxidative stress, lower mitochondrial DNA copy number, promote nuclear DNA damage and repair response, decrease mitochondrial respiratory chain enzyme activities, and upregulate Bcl-2 and caspase-3 gene expression in lymphocytes. We further revealed that Mycobacterium infection induces autophagy for selective sequestration and subsequent degradation of the dysfunctional mitochondrion before activating cellular apoptosis in the peripheral lymphocyte pool. Together, these observations uncover a new role of mitochondrial-nuclear crosstalk that apparently contributes to lymphocyte homeostasis in gastrointestinal tuberculosis infection.