An anti-inflammatory property of @entity5132 b-glucan: Induction of high levels of interleukin-1 receptor antagonist via a XXXX /CR3 independent mechanism.

@entity1 @entity1356 @entity9651 @entity1193 @entity5132
BACKGROUND: @entity5132 is an opportunistic fungal pathogen that induces strong proinflammatory responses, such as @entity1356 production. Much less is known about the induction of immune modulatory cytokines, such as the IL-1 receptor antagonist ( @entity1193 ) that is the main natural antagonist of IL-1, by @entity5132 . METHODS: Peripheral blood mononuclear cells (PBMC) of healthy individuals were stimulated with @entity5132 and different components of the fungal cell wall. The role of pathogen recognition receptors (PRRs) for the induction of @entity1356 and @entity1193 was investigated by using specific blockers or in PBMC from @entity9651 deficient @entity1 . RESULTS: @entity5132 induced a strong @entity1193 response, and this induction was primarily induced by the cell-wall component b-glucan. Blocking @entity1193 significantly increased @entity5132 b-glucan hyphae induced @entity1356 and IL-6 production. Surprisingly, blocking the b-glucan receptor @entity9651 or the downstream Syk or Raf-1 pathways only marginally reduced @entity5132 -induced @entity1193 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 @entity1193 production. PBMC isolated from @entity9651 deficient @entity1 produced normal @entity1193 amounts in response to @entity5132 stimulation. Interestingly, the @entity1193 synthesis induced by b-glucan was blocked by inhibitors of the Akt/PI3K pathway. CONCLUSIONS: b-glucan of @entity5132 induces a strong @entity1193 response, which is independent of the b-glucan receptors @entity9651 and CR3. These data strongly argue for the existence of an unknown b-glucan receptor that specifically induces an Akt/PI3K-dependent anti-inflammatory @entity1193 response upon recognition of @entity5132 .
