Enhancement of intracellular growth of Mycobacterium tuberculosis in human monocytes by transforming growth factor-beta 1.
The production of transforming growth factor-beta (TGF beta 1) by human monocytes (MN) infected with Mycobacterium tuberculosis and its effects on the intracellular fate of the organism were studied. M. tuberculosis infection of MN induced both expression of mRNA and secretion of tumor necrosis factor-alpha (TNF alpha) and TGF beta 1 protein. Neutralizing antibody to TGF beta 1 reduced the intracellular growth of M. tuberculosis. The growth-enhancing effects of TGF beta 1 could not be explained by increased initial bacterial load. Preculture with TGF beta 1 decreased uptake of M. tuberculosis. Exposure of MN to increasing concentrations of TGF beta 1 before or after infection with M. tuberculosis accelerated intracellular bacterial replication. Both TNF alpha and interferon-gamma (IFN-gamma) limited mycobacterial replication. TGF beta 1 (10 ng/mL) abrogated the bacteriostatic effects of TNF alpha and IFN-gamma. Within the infected focus, TGF beta 1 produced by mononuclear phagocytes may play an important role in the pathogenesis of tuberculosis, in part by modulating the response to potentially protective cytokines such as TNF alpha and IFN-gamma.
Department of Medicine, Case Western Reserve University, University Hospitals of Cleveland.
C S
CS
Hirsch
T
T
Yoneda
L
L
Averill
J J
JJ
Ellner
Z
Z
Toossi
D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D010587:Phagocytosis / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma