Induction of murine macrophage TNF-alpha synthesis by Mycobacterium avium is modulated through complement-dependent interaction via complement receptors 3 and 4 in relation to M. avium glycopeptidolipid

FEMS Microbiol Lett. 2005 May 15;246(2):221-8. doi: 10.1016/j.femsle.2005.04.008.

Abstract

We studied whether complement receptor (CR) mediated Mycobacterium avium interaction modulated macrophage TNF-alpha expression. Compared to control conditions, infections performed with C3-depletion yielded significantly higher TNF-alpha levels. Blockage of the CR4 iC3b site yielded increases in TNF-alpha for all morphotypic variants of a virulent serovar-8 strain (smooth transparent (SmT), smooth opaque (SmO), serovar-specific glycopeptidolipid (ssGPL) deficient knockout mutant) whereas CR3 blockage increased TNF-alpha only for SmT and ssGPL-deficient strains. Thus, complement-mediated binding of M. avium to CR3 and CR4 was shown to modulate TNF-alpha expression. The differential activation of morphotypic and isogenic variants of a single strain provides an excellent model system to delineate signaling pathways.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Complement C3 / metabolism*
  • Complement C4 / metabolism*
  • Glycolipids / genetics
  • Glycolipids / metabolism
  • Glycopeptides / genetics
  • Glycopeptides / metabolism
  • Humans
  • Macrophages / immunology*
  • Mice
  • Mycobacterium avium Complex / genetics
  • Mycobacterium avium Complex / immunology*
  • Mycobacterium avium Complex / metabolism
  • Mycobacterium avium-intracellulare Infection / immunology
  • Mycobacterium avium-intracellulare Infection / microbiology
  • Receptors, Complement / metabolism*
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Complement C3
  • Complement C4
  • Glycolipids
  • Glycopeptides
  • Receptors, Complement
  • Tumor Necrosis Factor-alpha