Mycobacterium tuberculosis-induced cell death of primary human monocytes and macrophages is not significantly modulated by tumor necrosis factor-targeted biologicals.
Differential induction of cell death in mycobacteria-infected monocytes and macrophages has been invoked as one possible mechanism by which some tumor necrosis factor (TNF)-targeted biologicals reactivate tuberculosis more frequently than others. We infected primary human monocytes and monocyte-derived macrophages with the virulent Mycobacterium tuberculosis strain H37Rv and followed the rate of cell death in the absence or presence of a wide concentration range of four different TNF-targeted biologicals: infliximab and adalimumab (both monoclonal antibodies to human TNF) and etanercept and polyethylene-glycols TNFR1 (fusion constructs of human TNFR2 and TNFR1, respectively). None of the TNF-targeted biologicals used modulated the death rate of monocytes/macrophages induced by infection with M. tuberculosis alone. Our data support the view that mycobacteria-induced cell death is largely independent of TNF and that the primary target for differential modulation by TNF-targeted biologicals during tuberculosis is not a recently recruited monocyte or freshly differentiated macrophage.
Reiling
Norbert
N
Division of Molecular Infection Biology, Department of Biochemical Microbiology, Research Center Borstel, Borstel, Germany.
Schneider
Dagmar
D
Ehlers
Stefan
S
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D016923:Cell Death; D002478:Cells, Cultured; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D000069285:Infliximab; D008264:Macrophages / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D009000:Monocytes / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity*; D011092:Polyethylene Glycols / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; C496217:PEGylated tumor necrosis factor alpha receptor 1; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept