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

J Infect Dis. 1994 Nov;170(5):1229-37. doi: 10.1093/infdis/170.5.1229.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Humans
  • Interferon-gamma / pharmacology
  • Monocytes / metabolism
  • Monocytes / microbiology*
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / growth & development
  • Phagocytosis / drug effects
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / pharmacology*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / pharmacology
  • Virus Replication / drug effects

Substances

  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma