FAS LIGAND-INDUCED APOPTOSIS OF INFECTED HUMAN MACROPHAGES REDUCES THE VIABILITY OF INTRACELLULAR MYCOBACTERIUM-TUBERCULOSIS

Mycobacterium tuberculosis-specific cytolytic activity is mediated mos tly by CD4(+) CTL in humans. CD4(+) CTL kill infected target cells by inducing Fas (APO-1/CD95)-mediated apoptosis. We have examined the eff ect of Fas ligand (Fas-L)-induced apoptosis of human macrophages infec ted in vitro with M. tuberculosis on the viability of the intracellula r bacilli, Human macrophages expressed Fas and underwent apoptosis aft er incubation with soluble recombinant Fast. in macrophages infected e ither with an attenuated (H37Ra) or with a virulent (H37Rv) strain of M. tuberculosis, the apoptotic death of macrophages was associated wit h a substantial reduction in bacillary viability. TNF-induced apoptosi s of infected macrophages was coupled with a similar reduction in myco bacterial viability, while the induction of nonapoptotic complement-in duced cell death had no effect on bacterial viable counts. infected ma crophages also showed a reduced susceptibility to Fast-induced apoptos is correlating with a reduced level of Fas expression. These data sugg est that apoptosis of infected macrophages induced through receptors o f the TNF family could be an immune effector mechanism not only depriv ing mycobacteria from their growth environment but also reducing viabl e bacterial counts bg an unknown mechanism. On the other hand, interfe rence by M. tuberculosis with the Fast system might represent an escap e mechanism of the bacteria attempting to evade the effect of apoptosi s.