A correlation between phagocytosis and apoptosis in THP-1 cells infected with prevalent strains of Mycobacterium tuberculosis

The innate ability of infected macrophages to undergo programmed cell death (apoptosis) and curtail the infection is crucial for the host defense. Although phagocytosis and intracellular killing mechanisms leading to apoptosis in macrophages are highly effective in eliminating the infecting tuberculous bacilli, some Mycobactetium tuberculosis (Mtb) strains have evolved strategies to inhibit this microbicidal function and make use of macrophage for its successful and prolonged survival. Two clinical strains of Mtb (S7 and S10) found to be prevalent and primitive, based on molecular epidemiological studies, were used to study the magnitude in induction of apoptosis in THP-1 cells at various time points of infection and to correlate it with phagocytosis. The percentage of phagocytosis did not show any strain-specific association with differentiated THP-1 cells. But in the phagocytic index, the clinical strains showed a low dose of infection in the 1-10 bacilli category thereby exerting less burden on the cells. The induction of apoptosis was strain dependent. The THP-1 cells infected with H37Ra and S10 showed an increase in apoptosis at all time points while the S7 strain induced minimum apoptosis. A negative correlation between apoptosis and phagocytic index was observed in the 1-10 category and a positive correlation in the > 20 category of the phagocytic index. This novel observation indicates that the magnitude of THP-1 cell apoptosis is a function of the number of internalized mycobacteria. These results indicated a differential mode of infection by clinical strains and their adaptation to different survival strategies that may lead to immune suppression and pathogenesis of the disease.