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

Abstract

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.

Extracellular Delivery of Functional Mitochondria Rescues the Dysfunction of CD4+T Cells in Aging

“…In short, mitochondrial dysfunction manifests as quantifiable abnormalities in the assembly of the ETC, mitochondrial membrane potential, excessive production of mitoROS, and abnormal production of ATP via Ox-Phos [24, 50, 53]. These perturbations impact the metabolic fitness and the redox-sensitive signaling pathways of CD4 + T cells [13, 25, 50, 54–57].…”

Mycobacterium tuberculosisESX-1-secreted substrate protein EspC promotes mycobacterial survival through endoplasmic reticulum stress-mediated apoptosis

“…The ER has a vital role in folding secretory and cellular proteins during their transit, and cellular disturbances cause misfolded/unfolded proteins to accumulate in the ER [27], which is referred to as ER stress. Mycobacterial infection can cause apoptosis mediated by interactions between uncontrolled ER stress and ROS [27][28][29]. Accordingly, we hypothesize that EspC might triggers ER stressmediated apoptosis.…”

Mapping the Mitochondrial Regulation of Epigenetic Modifications in Association With Carcinogenic and Noncarcinogenic Polycyclic Aromatic Hydrocarbon Exposure

“…Then, 1 × 10 6 viable cells were cultured with HiKar-yoXL RPMI media in 5% CO 2 atmosphere at 37°C for 24 hours. 19 The cells were exposed to PAHs for 0 hours, 30 minutes, 1, 3, 6, 12, 24, 48, and 72 hours to assess different parameters, while DMSO (0.1%) treated cells were used as controls.…”