An anti-inflammatory property of Candida albicans beta-glucan: Induction of high levels of interleukin-1 receptor antagonist via a Dectin-1/CR3 independent mechanism

作者：Smeekens Sanne P; Gresnigt Mark S; Becker Katharina L; Cheng Shih Chin; Netea Stejara A; Jacobs Lie**eth; Jansen Trees; van de Veerdonk Frank L; Williams David L; Joosten Leo A B; Dinarello Charles A; Netea Mihai G^*

来源：Cytokine, 2015, 71(2): 215-222.

DOI：10.1016/j.cyto.2014.10.013

• beta-Glucan
• IL-1Ra
• Candida albicans

Background: Candida albicans is an opportunistic fungal pathogen that induces strong proinflammatory responses, such as IL-I beta production. Much less is known about the induction of immune modulatory cytokines,*such as the IL-1 receptor antagonist (IL-1Ra) that is the main natural antagonist of IL-1, by C. albicans.
Methods: Peripheral blood mononuclear cells (PBMC) of healthy individuals were stimulated with C albicans and different components of the fungal cell wall. The role of pathogen recognition receptors (PRRs) for the induction of IL-1 beta and IL-1Ra was investigated by using specific blockers or in PBMC from Dectin-1 deficient patients.
Results: C. albicans induced a strong IL-1Ra response, and this induction was primarily induced by the cell-wall component beta-glucan. Blocking IL-1Ra significantly increased C albicans p-glucan hyphae induced IL-1 beta and IL-6 production. Surprisingly, blocking the p-glucan receptor Dectin-1 or the downstream Syk or Raf-1 pathways only marginally reduced C. albicans-induced IL-1Ra production, while blocking of the complement receptor 3 (CR3), TLR2 or TLR4 had no effect. In line with this, blocking MAP kinases had little effect on Candida-induced IL-1Ra production. PBMC isolated from Dectin-1 deficient patients produced normal IL-1Ra amounts in response to C. albicans stimulation. Interestingly, the IL-1Ra synthesis induced by beta-glucan was blocked by inhibitors of the Akt/PI3 K pathway.
Conclusions: beta-glucan of C albicans induces a strong IL-1Ra response, which is independent of the p-glucan receptors dectin-1 and CR3. These data strongly argue for the existence of an unknown beta-glucan receptor that specifically induces an Akt/PI3 K-dependent anti-inflammatory IL-1Ra response upon recognition of C albicans. 2014 Elsevier Ltd.

• 出版日期2015-2