Involvement of caspase-3, lipid peroxidation and TNF-α in causing apoptosis of macrophages by coordinately expressed Salmonella phenotype under stress conditions

Abstract: Invasive Salmonella has been reported to induce apoptosis of macrophages as a part of its infection process, which may allow it to avoid detection by the innate immune system. However, the bacterial components capable of inducing apoptosis, particularly under the environments offered by the host have not been fully identified. Therefore, in the present study, attempts were made to evaluate the apoptotic potential of Salmonella enterica serovar Typhi (S. typhi) outer membrane protein expressed under stress conditions like iron, oxidative and anaerobic simulating the in vivo situations encountered by the pathogen. Analysis of data revealed that a coordinately expressed 69kDa outer membrane protein (OMP) expressed with enhanced intensity under iron, oxidative and anaerobic stress conditions caused apoptotic cell death in 51% of macrophages, whereas OMPs of S. typhi extracted under normal conditions accounted for apoptotic cell death in only 31% of macrophages. A significantly enhanced activity of caspase-3 was observed during macrophage-apoptosis induced by this protein. A significant increase in the extent of lipid peroxidation (levels of oxidant) and decrease in the activities of antioxidants was also observed which correlated with the increased generation of tumor necrosis factor-α, interleukine-1α and interleukine-6. These results suggest that caspase-3 and tumor necrosis factor-α in conjunction with other cytokines may induce apoptotic cell death through the up-regulation of oxidants and down-regulation of antioxidants. These findings may be relevant for the better understanding of the disease pathophysiology and for the future developments of diagnostic and preventive strategies during the host–pathogen interactions. [Copyright &y& Elsevier]