Mycobacterium bovis Bacillus Calmette Guérin infection prevents apoptosis of resting human monocytes.
Apoptosis plays an essential role in the development and homeostasis of multicellular organisms. Some infectious agents interfere with this programmed cell death to their own benefit. Here, we show that infection of resting human monocytes with Mycobacterium bovis Bacillus Calmette Guérin (BCG) increases monocyte viability by preventing them from undergoing apoptosis. Heat-killed BCG also prevented apoptosis, indicating that replication of BCG is not required to prevent cell death. Analysis of BCG-infected monocytes revealed an up-regulation of the A1 mRNA, whereas the bcl-2 mRNA was not up-regulated. Interestingly, preinfection with BCG renders the cells resistant to interleukin (IL)-10-induced apoptosis which may be one of the mechanisms mycobacteria use to modulate immune responses. BCG infection was also accompanied by an impairment of the capacity of monocytes to secrete IL-10 and by an induction of the capacity to secrete tumor necrosis factor-alpha, two cytokines known to induce and prevent human monocyte apoptosis, respectively. 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.
Kremer
L
L
Laboratoire de Microbiologie Génétique et Moléculaire, INSERM U447, Institut Pasteur de Lille, France.
Estaquier
J
J
Brandt
E
E
Ameisen
J C
JC
Locht
C
C
D017209:Apoptosis; D001500:BCG Vaccine / Q000276:immunology*; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004268:DNA-Binding Proteins / Q000378:metabolism; D018398:Homeodomain Proteins; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D015778:Minor Histocompatibility Antigens; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D051818:Replication Protein C; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D001500:BCG Vaccine; C096816:BCL2-related protein A1; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D008070:Lipopolysaccharides; C096063:MATA1 protein, S cerevisiae; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D051818:Replication Protein C