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

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