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Cytokine response to inactivated Candida albicans in mice
E Rosati1, L Scaringi, P Cornacchione
1Department of Clinical Medicine, University of Perugia, Policlinico Monteluce, Italy.
Abstract:
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 -14, -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-1 beta mRNAs while genes coding for IL-4, IL-5, IL-6, IL-10, IL-12, TNF alpha, and IFN gamma were not expressed and there was a high level of NK activity. Two hours after CA-5d a high level of IFN gamma and a low level of IL-10 mRNAs were already evident, while IL-2 and much more IL-1 beta had greatly increased. IL-6, TNF alpha, and IL-2R alpha 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-1 beta and IFN gamma 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-1 beta mRNA expression had further decreased. These results indicate that CA induces a predominant production of IFN gamma 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 in the development of TH1 response, is probably the result of the ability of IL-2, IL-1 beta, and TNF alpha to synergize in inducing IFN gamma synthesis by NK cells.
Insights
Inactivated Candida albicans (CA) strongly activates natural killer (NK) cells and induces T-helper 1 (TH1) immune responses, primarily through interferon-gamma (IFN-γ) and interleukin-2 (IL-2) production, without involving IL-12.
Area of Science:
- Immunology
- Microbiology
- Cellular Biology
Background:
- Inactivated Candida albicans (CA) are known to activate natural cytotoxic effectors in mice.
- Cytokine production by natural immune cells is crucial for regulating T-helper (TH) responses.
- Understanding the cytokine gene expression profile following CA challenge is key to elucidating immune mechanisms.
Purpose of the Study:
- To investigate the expression of cytokine genes involved in the immune response to inactivated Candida albicans.
- To determine the role of specific cytokines, particularly IL-12, in the development of TH1 responses induced by CA.
- To analyze the kinetics of cytokine mRNA expression and natural killer (NK) cell activity post-CA administration.
Main Methods:
- Northern blot analysis was used to assess cytokine gene expression in peritoneal exudate cells (PEC) from mice.
- Mice were injected with inactivated CA cells (CA-5d or CA-4d) at specific time points before in vitro assays.
- Natural killer (NK) cell activity and lymphokine-activated killer (LAK) activity were measured.
Main Results:
- CA administration led to high expression of IL-2 and IFN-γ mRNA, and significant NK cell activity.
- IL-12 mRNA was notably absent throughout the CA sensitization and challenge periods.
- IL-2, IL-1β, and TNF-α were found to synergize in inducing IFN-γ synthesis by NK cells, suggesting an alternative TH1 pathway.
Conclusions:
- Inactivated CA induces a predominant TH1-biased immune response characterized by IFN-γ and IL-2 production.
- The absence of IL-12 induction suggests a distinct, IL-12-independent pathway for TH1 development in response to CA.
- The synergistic action of IL-2, IL-1β, and TNF-α on NK cells highlights a unique mechanism for IFN-γ generation.