Apoptosis, but not necrosis, of infected monocytes is coupled with killing of intracellular bacillus Calmette-Guérin.

Abstract

SllmmsryWe have examined the effect of killing of host monocytes infected with bacillus Calmette-Gu6rin (BCG) on the viability of the intracellular mycobacteria. Peripheral blood monocytes were infected in vitro with a single bacillus per cell and maintained in culture for 6-8 d to allow the bacilli to replicate. Replicating viable BCG were found singly in perinuclear vacuoles bounded by tightly apposed lipid bilayers. Monocytes were then exposed to toxic mediators that induced killing of cells as evaluated by StCr release into the culture medium. Both hydrogen peroxide (H202) (an inducer of cell necrosis) and adenosine triphosphate (ATP 4-) (an inducer of cell apoptosis) treatment killed infected monocytes. H202-induced killing had no effect on BCG viability. ATPinduced cell death was accompanied by DNA fragmentation and nuclear condensation. Apoptosis was associated with a swelling of the phagocytic vacuoles which became multibacillary and with a reduction of BCG viability as enumerated by colony-forming units.

Macrophage and T lymphocyte apoptosis during experimental pulmonary tuberculosis: their relationship to mycobacterial virulence

“…Several in vitro studies have demonstrated that alveolar macrophages undergo apoptosis following infection with M. tuberculosis [2][3][4][5][6][7][8], and apoptosis of these infected macrophages may benefit the host by eliminating the favorable environment for bacterial growth [4,5]. Furthermore, these in vitro studies have also demonstrated that infected macrophage apoptosis was TNF-a dependent, and virulent strains, such as H37Rv, induce lesser macrophage apoptosis than the isogenic avirulent strain H37Ra [5].…”

“…Intracellular microorganisms that are able to multiply within macrophages, such as Mycobacterium tuberculosis, are efficient inducers of apoptosis, and it has been demonstrated that apoptosis, but not necrosis, is associated with killing of intracellular mycobacteria [2,3]. Thus, it has been hypothesized that inhibiting apoptosis of macrophages might be a survival strategy for virulent mycobacteria [4].…”

ChlamydiapneumoniaeInhibits Apoptosis in Human Peripheral Blood Mononuclear Cells Through Induction of IL-10

“…Moreover, other biological processes such as host defense against viral (1-3) and bacterial (4,5) infections may depend critically upon apoptotic events for the normal processing of microbes (6,7). Many intracellular organisms rely on host cells to survive and propagate; therefore, it is advantageous for them to develop strategies to inhibit host cell apoptosis.…”

Role of CD8+ and WC-1+ γ/δ T cells in resistance to Mycobacterium bovis infection in the SCID-bo mouse

“…A second potential role for CD8 ϩ T cells is to mediate a terminal bactericidal event via cytolysis directed against chronically infected cells. Several studies with mouse and human CD8 ϩ or CD4 ϩ effector cells suggest that species differences in pathways mediating a terminal mycobactericidal effector pathway may exist, although apoptotic death of the target cell appears to be a common feature [9][10][11]. The precise effector role(s) and contribution of bovine CD8 ϩ T cells in resistance to mycobacterial infection remains to be fully elucidated in vitro and in vivo.…”