INTERLEUKIN-15 INDUCES ANTIMICROBIAL ACTIVITY AFTER RELEASE BY CRYPTOCOCCUS-NEOFORMANS STIMULATED MONOCYTES

A newly described cytokine, interleukin (IL)-15, shares many activitie s with IL-2; however, little is known about the stimuli for release of IL-15, and its role in antimicrobial host defense has not previously been demonstrated. This study found that Cryptococcus neoformans is a potent stimulus for the release of biologically active IL-15 from mono cytes. Both IL-15 and IL-2 made significant contributions to lymphocyt e proliferation and lymphocyte-mediated anticryptococcal activity to e ncapsulated and acapsular C. neoformans. IL-15 restored lymphocyte pro liferation and anticryptococcal activity that had been abrogated by bl ocking IL-2. IL-15 also enhanced the anticryptococcal activity of lymp hocytes but did not enhance the activity of monocytes. This suggests t hat IL-15 and IL-2 cooperate for lymphocyte activation and proliferati on in vitro and demonstrates that IL-15 can induce antimicrobial activ ity, Taken together, these data suggest that microbes, and in particul ar C. neoformans, are an important stimulus for IL-15 and that IL-15 m ay have an important role in induction of antimicrobial effector mecha nisms.