Concurrent infection of human macrophages with HIV-1 and Mycobacterium avium results in decreased cell viability, increased M. avium multiplication and altered cytokine production.

The effects of a concurrent HIV-1 and Mycobacterium avium infection in vitro were assessed in human peripheral blood-derived macrophages (M phi). M phi were infected with HIV-1Ba-L strain for 14 days then infected with M. avium (HIV/M. avium) or treated with LPS (HIV/LPS). At various times after M. avium or LPS treatment, Mo phi cultures were harvested for quantitation of HIV and M. avium replication, as well as M phi cellular viability. In addition, mRNA and supernatants were collected for assessment of induction of the cytokines TNF-alpha, IL-1 beta and IL-6. M. avium multiplication was greater in HIV-infected M phi, whereas no difference in virus production, based on p24 and RT values, was observed between HIV-infected cells and HIV/M. avium or HIV/LPS M phi. M. avium infection of HIV-1-infected M phi also caused a decrease in viability of the M phi. HIV-1/M. avium-infected M phi had a 24 h delay in induction of TNF-alpha steady state mRNA when compared with HIV/LPS or M. avium only or LPS-only treated M phi. HIV infection also increased the amount and the length of induction of IL-1 beta and IL-6 steady state mRNA stimulated by either M. avium or LPS. In addition, prolonged and increased protein production of TNF-alpha, IL-6, and IL-1 beta was observed in HIV/M. avium-infected cells when compared with the other treatments. In direct contrast to M. avium infection, no significant differences in LPS-induced protein production of the three cytokines was observed between HIV-1-infected and -noninfected M phi. Treatment of HIV/M. avium-infected cells with human rGM-CSF did not increase either the time or quantity of induction of TNF-alpha mRNA or protein production in HIV/M. avium-infected M phi. The increase in M. avium numbers, dysregulation of cytokine production, and subsequent cell death seen in vitro in HIV/M. avium-infected human M phi may reflect part of the underlying cause of the highly disseminated M. avium disease pattern observed in AIDS patients.