Enhancement of intracellular growth of Mycobacterium tuberculosis in human monocytes by transforming growth factor-beta 1. 1994

C S Hirsch, and T Yoneda, and L Averill, and J J Ellner, and Z Toossi
Department of Medicine, Case Western Reserve University, University Hospitals of Cleveland.

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.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D009169 Mycobacterium tuberculosis A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation. Mycobacterium tuberculosis H37Rv
D010587 Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES). Phagocytoses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D014779 Virus Replication The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle. Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
D016212 Transforming Growth Factor beta A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. Bone-Derived Transforming Growth Factor,Platelet Transforming Growth Factor,TGF-beta,Milk Growth Factor,TGFbeta,Bone Derived Transforming Growth Factor,Factor, Milk Growth,Growth Factor, Milk

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