MYCOBACTERIUM-AVIUM-INTRACELLULARE COMPLEX ACTIVATES NUCLEAR TRANSCRIPTION FACTOR-KAPPA-B IN DIFFERENT CELL-TYPES THROUGH REACTIVE OXYGEN INTERMEDIATES

Myeobacterium avium-intracellulare complex (MAC) is one of the most co mmon opportunistic pathogens in HIV-infected patients. Their synergist ic interaction leads to a rapid deterioration of the host defense. In vivo, MAC manifests as a disseminated granulomatous disease that produ ces a massive inflammatory tissue response perhaps through its activat ion of inflammatory cytokines. The intracellular signaling following i nteraction of the mycobacterium with host cells is incompletely unders tood, Because the response is dependent, in part, on the activation of NF-kappa B, we investigated the effect of MAC on this nuclear transcr iption factor in cells of macrophage and nonmacrophage lineage, We dem onstrate that both high and low virulence strains of. MAC potently and rapidly activated NF-kappa B, In supershift assays, using specific Ab s against the NF-kappa B subunit's, we identified a p50/p65 heterodime r that was formed within 5 min after incubation with the bacterium too rapidly for cytokines to be involved in the activation. This activati on was instead mediated through the generation of reactive oxygen inte rmediates, inasmuch as preincubation of cells with a variety of antiox idants inhibited NF-kappa B activation. Likewise, the transfection of cells with Mn-superoxide dismutase blocked the NF-kappa B activation i nduced by the bacterium. These data suggest that NF-kappa B activation is a consequence of interaction of host cells with the bacterium and that the interaction may play a pivotal Pole in the pathogenesis of th e disease.