Interleukin 10 produced by macrophages inoculated with Mycobacterium avium attenuates mycobacteria-induced apoptosis by reduction of TNF-alpha activity.
Normal human macrophages respond to infection with Mycobacterium avium, serovar 4, by producing tumor necrosis factor (TNF)-alpha, which mediates apoptosis, and by elaborating interleukin (IL)-10, a TNF-alpha antagonist. We show that IL-10 down-regulates apoptosis by inhibiting the TNF-alpha production of the inoculated macrophages and by inducing the release of soluble TNF receptor type 2 from the macrophages, which leads to inactivation of TNF-alpha. These experiments suggest that induction of IL-10 production is a virulence factor that creates an intracellular sanctuary for the bacteria that is inaccessible to the defense mechanisms of the host.
Balcewicz-Sablinska
M K
MK
Division of Rheumatology, Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Gan
H
H
Remold
H G
HG
D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology*; D007700:Kinetics; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D015269:Mycobacterium avium Complex / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000502:physiology; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10