Cytokine Response to Inactivated Candida albicans in Mice

Inactivated Candida albicans (CA) cells induce strong activation of natural cytotoxic effectors in mice. In the present study we examined the expression of cytokine genes involved in the immune response to CA. It has been reported that differential cytokine production by natural immune cells is important for regulating the development of specific TH response. Northern blot analysis was performed on peritoneal exudate cells (PEC) recovered from CD2F1 mice injected ip with five doses of CA (CA-5d, on Days - 1d, -10, -7, -3,0 with respect to the in vitro assays at 2, 24, and 72 hr) or from mice injected ip with four doses of CA (CA-4d, on Days -14, -10, -7, -3 with respect to the in vitro assay on Day 0). On Day 0, before the fifth CA injection, PEC expressed a high level of IL-2 and a low level of IL-1β mRNAs while genes coding for IL-4, IL-5, IL-6, IL-10, IL-12, TNFα, and IFNγ were not expressed and there was a high level of NK activity. Two hours after CA-5d a high level of IFNγ and a low level of IL-10 mRNAs were already evident, while IL-2 and much more IL-1β had greatly increased. IL-6, TNFα, and IL-2Rα chain mRNAs were also detectable, whereas IL-4, IL-5, and IL-12 were not expressed. IL-12 mRNA was also absent in earlier stages of the CA sensitization. Both cellularity and NK activity of peritoneal exudate had increased with respect to Day 0. At 24 hr whereas IL-2 mRNA remained high, both IL-1β and IFNγ mRNAs expression had decreased. Expression of other cytokines was no longer detectable but NK activity remained high and a significant LAK activity was also induced. After 72 hr, while the IL-2 mRNA level and NK activity were still high the IL-1β mRNA expression had further decreased. These results indicate that CA induces a predominant production of IFNγ and IL-2, cytokines involved in the development of TH1 response but it is unable to induce IL-12. This secondary pathway, without IL-12 involvement ill the development of TH1 response, is probably the result of the ability of IL-2, IL-1β, and TNFα to synergize in inducing IFNγ synthesis by NK cells.