GROWTH OF MYCOBACTERIUM-AVIUM IN HUMAN MONOCYTES - IDENTIFICATION OF CYTOKINES WHICH REDUCE AND ENHANCE INTRACELLULAR MICROBIAL-GROWTH

Human monocytes were isolated by standard procedures and their ability to harbor growth of two virulent strains of Mycobacterium avium, TMC724 and TMC7479, was assessed in the absence or presence of cytokines. Both strains of mycobacteria, especially the M. avium TMC7479, grew progressively in untreated human monocytes. Inclusion of certain macrophage-activating cytokines, such as interferon-gamma in the presence of indomethacin or 1,25(OH2)-vitamin D3 (calcitriol) led to significant reductions in bacterial growth at 7 days post-infection. Conversely, treatment of human monocytes with interleukin-(IL) 1, macrophage-colony stimulating factor or IL 3 led to an increased permissiveness of these cells for M. avium. Moreover, these cytokines were shown to increase dramatically extracellular M. avium growth in vitro in tissue culture medium. Further, inclusion of antibodies against IL 1-beta and IL 6 in untreated infected monocytes monolayers led to a reduced growth of M. avium, suggesting that infected monocytes produce factors which enhance their susceptibility to M. avium. Overall, my findings suggest that cytokines may play a bidirectional role in atypical mycobacterial infections, by either increasing or decreasing resistance of the monocyte.