MYCOBACTERIUM-BOVIS BACILLUS-CALMETTE-GUERIN INFECTION PREVENTS APOPTOSIS OF RESTING HUMAN MONOCYTES

Apoptosis plays an essential role in the development and homeostasis o f multicellular organisms. Some infectious agents interfere with this programmed cell death to their own benefit. Here, we show that infecti on of resting human monocytes with Mycobacterium bovis Bacillus Calmet te Guerin (BCG) increases monocyte viability by preventing them from u ndergoing apoptosis. Heat-killed BCG also prevented apoptosis, indicat ing that replication of BCG is not required to prevent cell death. Ana lysis of BCG-infected monocytes revealed an up-regulation of the A1 mR NA, whereas the bcl-2 mRNA was not up-regulated, interestingly, preinf ection with BCG renders the cells resistant to interleukin (IL)-10-ind uced apoptosis which may be one of the mechanisms mycobacteria use to modulate immune responses. BCG infection was also accompanied by an im pairment of the capacity of monocytes to secrete IL-10 and by an induc tion of the capacity to secrete tumor necrosis factor-alpha, two cytok ines known to induce and prevent human monocyte apoptosis, respectivel y. Since it has been reported that apoptosis is involved in killing of intracellular mycobacteria, the prevention of apoptosis may represent a strategy for mycobacterial survival in the infected host.