Innate Cellular Immunity in Newly Diagnosed Pulmonary Tuberculosis Patients and During Chemotherapy

BACKGROUND Leukocyte migration (LM) and intracellular killing aspects of the innate immune response play important roles in protection against and containment and cure of Mycobacterium tuberculosis infection, and thus may be exploited as immunotherapeutic targets to improve the management and treatment outcomes of patients with tuberculosis (TB). OBJECTIVES The aim of this study was to assess LM and mediators of intracellular killing in patients with TB at the time of diagnosis and during anti-TB chemotherapy and compare them with apparently healthy controls. METHODS We recruited 24 patients who were newly diagnosed with pulmonary TB and 20 apparently healthy individuals. Blood was drawn from patients with TB at the time of diagnosis, and after 2, 4, and 6 months of anti-TB chemotherapy and control. In vitro percentage LM (%LM) upon stimulation with Bacillus Calmette-Guerin vaccine, percentage nitroblue tetrazolium (%NBT) reduction, plasma concentrations of hydrogen peroxide (H2O2), and nitric oxide (NO) were assessed in both groups. FINDINGS Percentage NBT was significantly reduced in patients with TB at 2 months of anti-TB chemotherapy compared with patients at diagnosis and in healthy controls, whereas % LM was significantly increased in patients at 4 months of anti-TB chemotherapy compared with patients at diagnosis and controls. Mean plasma H2O2 and NO were significantly reduced in patients at diagnosis and throughout the period of anti-TB chemotherapy compared with the control group. Significant decreases were demonstrated in mean plasma H2O2 and NO in patients at 2 and 4 months of anti-TB chemotherapy, respectively, compared with patients at diagnosis. There was significant positive correlation between % NBT with plasma H2O2 and NO, but % LM was negatively correlated with plasma H2O2 in this group. CONCLUSION The intracellular killing aspect of innate cellular immunity is deficient in patients with TB, especially 2 to 4 months after commencement of treatment. Therefore, measures (eg, arginine supplementation) to improve intracellular killing in these patients is advocated. Moreover, % LM assay with Bacillus Calmette-Guerin vaccine as an antigen may be used to differentiate those newly diagnosed patients from those on anti-TB chemotherapy.