Modulation of IL-12 by transforming growth factor-beta (TGF-beta) in Mycobacterium tuberculosis-infected mononuclear phagocytes and in patients with active tuberculosis.
In humans, tuberculosis is associated with suppression of T-cell responses to antigens of Mycobacterium tuberculosis. Recently, the macrophage product, transforming growth factor-beta (TGF-beta) has been implicated in suppression of T-cell proliferation and cytokine production during tuberculosis. We studied the effect of TGF-beta on production of IL-12, and on the augmentation of M. tuberculosis-induced IFN gamma production by IL-12, in patients with pulmonary tuberculosis and by M. tuberculosis. Induction of IL-12 p35, but not IL-12 p40, by M. tuberculosis in monocytes was dependent on prior priming of the cells with IFN gamma. Expression of both IL-12 p40 and p35, however, was suppressed by TGF-beta. Further, TGF-beta interfered with the bioactivity of IL-12 in the enhancement of M. tuberculosis-induced IFN gamma mRNA expression and cytokine production. However, in mononuclear cells from patients with tuberculosis the main effect of TGF-beta on IL-12 appeared to be counter action to IL-12 induced IFN gamma production in response to M. tuberculosis.
Toossi
Z
Z
Division of Infectious Diseases, Case Western Reserve University, Cleveland, Ohio 44106, USA. zxt2@pocwruedu
Mincek
M
M
Seeholtzer
E
E
Fulton
S A
SA
Hamilton
B D
BD
Hirsch
C S
CS
D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000473:pathology*
D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D018664:Interleukin-12; D007371:Interferon-gamma