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Specific activated T cells regulate IL-12 production by human monocytes stimulated with Cryptococcus neoformans
C Retini1, A Casadevall, D Pietrella
1Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Journal of Immunology (Baltimore, Md. : 1950)
|February 11, 1999
Summary
Human monocytes produce interleukin-12 (IL-12) through T cell-dependent and independent pathways when exposed to Cryptococcus neoformans. Monocyte IL-12 secretion is enhanced by T cell interaction, particularly via CD40 signaling.
Area of Science:
- Immunology
- Microbiology
Background:
- Interleukin-12 (IL-12) is a critical cytokine in immune responses.
- Understanding IL-12 production by human monocytes against fungal pathogens like Cryptococcus neoformans is crucial for developing effective immunotherapies.
Purpose of the Study:
- To investigate the pathways of IL-12 production by human monocytes in response to Cryptococcus neoformans.
- To elucidate the roles of T cells, CD40 signaling, and IFN-gamma in this process.
Main Methods:
- Primary human monocytes were stimulated with encapsulated and acapsular Cryptococcus neoformans and Candida albicans.
- Monocytes were co-cultured with activated T cells specific for C. neoformans.
- IL-12 levels were measured using ELISA.
- Monoclonal antibodies targeting glucuronoxylomannan and Fc cross-linking were employed.
- Flow cytometry was used to assess CD40 and CD40 ligand expression.
Main Results:
- Freshly isolated monocytes produced IL-12 within 24-48 hours when stimulated with acapsular C. neoformans or Candida albicans.
- Monocytes alone produced minimal IL-12 in response to encapsulated C. neoformans.
- IL-12 secretion was enhanced by anti-glucuronoxylomannan mAb and Fc cross-linking.
- Consistent IL-12 secretion was observed when monocytes were co-cultured with activated T cells, peaking at 5-7 days.
- Endogenous IFN-gamma strongly regulated IL-12 secretion.
- The interaction between CD40 on monocytes and CD40 ligand on T cells was critical for IL-12 secretion.
Conclusions:
- Human monocytes exhibit biphasic IL-12 secretion in response to C. neoformans.
- An early, T cell-independent pathway is driven by direct fungal insult.
- A later, T cell-dependent pathway involves CD40-CD40 ligand interactions and IFN-gamma, leading to sustained IL-12 production.