REGULATION OF MACROPHAGE ACTIVATION AND HUMAN-IMMUNODEFICIENCY-VIRUS PRODUCTION BY INVASIVE SALMONELLA STRAINS

Salmonellae possess the ability to adhere to and invade macrophages an d in so doing trigger a number of intracellular events that are associ ated with cellular activation, As an initial approach to defining the mechanisms by which invasive salmonellae alter macrophage function, we have explored the impact of Salmonella infection on the production of human immunodeficiency virus (HIV) in U1 cells, a promonocytic cell l ine latently infected with the virus. Infection of U1 cells with a pat hogenic strain of Salmonella enteritidis resulted in a marked inductio n of macrophage activation and HIV production. The stimulatory effect of salmonellae was mediated by signals other than lipopolysaccharide. Salmonella mutants with specific defects in invasion or intracellular survival were markedly less effective in the induction of HIV producti on. In contrast to S. enteritidis, strains of Yersinia enterocolitica, Legionella pneumophila, and Escherichia coli did not induce HIV produ ction. However, all of these bacteria induced comparable levels of gen e expression mediated by the HIV long terminal repeat. The results of this study are consistent with the notion that invasive salmonellae po ssess the ability to activate the macrophage by at least one mechanism that is not shared with several other species of gram-negative bacter ia. Furthermore, the expression of this unique property is maximal wit h Salmonella strains that are not only invasive but also capable of pr olonged survival within the macrophage. Our results indicate that the U1 cell line may be a very useful model system with which to examine t he biochemical pathways by which internalized salmonellae modulate the activation state of the macrophage.