Mycobacterium tuberculosis (MTB) is one of the most successful pathogens in human history and remains a global health challenge. MTB has evolved a plethora of strategies to evade the immune response sufficiently to survive within the macrophage in a bacterial-immunological equilibrium, yet causes sufficient immunopathology to facilitate its transmission. This review highlights MTB as the driver of disease pathogenesis and presents evidence of the mechanisms by which MTB manipulates the protective immune response into a pathological productive infection.

Sutherlandia frutescens (SF), a medicinal plant indigenous to South Africa, is traditionally used to treat a diverse range of illnesses, including cancer and viral infections. The biologically active compounds of SF are polar, thus renal elimination increases susceptibility to toxicity in that organ. This study investigated the antioxidant potential, lipid peroxidation, mitochondrial membrane potential and apoptotic induction by SF extracts on proximal and distal tubule epithelial cells. Cell viability was determined using the MTT assay. Mitochondrial membrane potential was determined using a flow cytometric JC-1 Mitoscreen assay. Cellular glutathione and apoptosis were measured using the GSH-Glo™ Glutathione assay and Caspase-Glo® 3/7 assay, respectively. The IC50 values from the cell viability results for LLC-PK1 and MDBK were 15 mg/mL and 7 mg/mL, respectively. SF extracts significantly decreased intracellular glutathione in LLC-PK1 (p less than 0.0001) and MDBK (p less than 0.0001) cells, while lipid peroxidation increased in treated LLC-PK1 (p less than 0.0001) and MDBK (p less than 0.0001) cells. JC-1 analysis showed that SF extracts promoted mitochondrial membrane depolarization in both LLC-PK1 and MDBK cells by up to 80% (p less than 0.0001). The activity of caspase 3/7 increased in both LLC-PK1 (11.9-fold; p less than 0.0001) and MDBK (2.2-fold; p less than 0.0001) cells. SF extracts at high concentrations appear to increase oxidative stress, to alter mitochondrial membrane integrity, and to promote apoptosis in renal tubule epithelia.

Background: Interleukin-6 (IL-6) is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases such as coronary artery disease (CAD). The −174 IL-6 G/C promoter polymorphism influences mRNA levels and protein expression and is implicated in CAD. The Indian population in South Africa, unlike the black community, has a high prevalence of premature CAD. This polymorphism has not been fully explored in this population. The present study assessed the −174 IL-6 G/C polymorphism in young Indian patients with angiographically documented CAD and compared them with age- and gender-matched Indian and black control subjects. Methods: Polymorphic variants were assessed by polymerase chain reaction–restriction fragment length polymorphism, and IL-6 levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: The −174 IL-6 C allele was found with a higher frequency (23%) in the total Indian group compared to 2% in the black participants [ P <0.0001, odds ratio (OR)=0.05, 95% confidence interval (CI) 0.018–0.14). The difference in frequency was more pronounced when Indian controls were compared to black controls (29% vs. 2%, respectively) ( P <0.0001, OR=0.05, 95% CI 0.02–0.17). A significant association between the −174 IL-6 G allele and CAD was found in Indian patients compared to Indian controls (84% in cases vs. 71% in Indian controls; P =0.043, OR=0.47 95% CI 0.23–0.95). Levels of IL-6 in circulation were higher in black controls (6.62±0.63 pg/mL) compared to Indian controls (2.51±0.57 pg/mL) and CAD patients (1.46±0.36 pg/mL) ( P <0.0001). Levels of IL-6 were higher in all groups with homozygous −174 IL-6 C alleles, but only significant in the healthy Indian control group (GG 3.73±0.94 pg/mL vs. GC/CC 0.89±0.5 pg/mL, P =0.0001). Conclusion: The presence of the IL-6 −174 G allele influences levels of IL-6 and increases the risk of CAD in South African Indians.