Interleukin-15 Induces Antimicrobial Activity after Release by Cryptococcus neoformans-Stimulated Monocytes

A newly described cytokine, interleukin (IL)-15, shares many activities 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 monocytes. Both IL-15 and IL-2 made significant contributions to lymphocyte proliferation and lymphocyte-mediated anticryptococcal activity to encapsulated and acapsular C. neoformans. IL-15 restored lymphocyte proliferation and anticryptococcal activity that had been abrogated by blocking IL-2. IL-15 also enhanced the anticryptococcal activity of lymphocytes but did not enhance the activity of monocytes. This suggests that IL-15 and IL-2 cooperate for lymphocyte activation and proliferation in vitro and demonstrates that IL-15 can induce antimicrobial activity. Taken together, these data suggest that microbes, and in particular C. neoformans, are an important stimulus for IL-15 and that IL-15 may have an important role in induction of antimicrobial effector mechanisms.