Induction of Mycobacterium avium growth restriction and inhibition of phagosome-endosome interactions during macrophage during macrophage activation and apoptosis induction by picolinic acid plus IFNγ

Treatment of mouse macrophages with picolinic acid (PA) and γ-interferon (IFN) led to the restriction of Mycobacterium avium proliferation concomitant with the sequential acquisition of metabolic changes typical of apoptosis, mitochondrial depolarization, annexin V staining and caspase activation, over a period of up to 5 days. However, triggering of cell death by ATP, staurosporine or H₂O₂ failed to affect mycobacterial viability. In contrast to untreated macrophages where extensive interactions between phagosomes and endosomes were observed, phagosomes from treated macrophages lost the ability to acquire endosomal dextran. N-Acetylcysteine was able to revert both the anti-mycobacterial activity of treated macrophages as well as the block in phagosome-endosome interactions. The treatment, however, induced only a minor increase in the acquisition of lysosomal markers, namely Lamp-1, and did not increase to any great extent the acidification of the phagosomes. These data thus suggest that the anti-mycobacterial activity of PA and IFNγ depends on the interruption of intracellular vesicular trafficking, namely the blocking of acquisition of endosomal material by the microbe.