β-glucans as conductors of immune symphonies

The use of immunostimulants has received increased attention due to the discovery of Toll-like receptors (TLR) or/and pattern recognition receptors (PRR). These receptors have been found to bind molecules from a range of pathogens including self-molecules. When cell damage has occurred many of the released molecular structures act as so-called "danger" signals possessing pathogen-associated molecular patterns (PAMP). These danger signals often consist of repeating molecular moieties yielding high molecular weight compounds. Examples are beta-glucans and CpG containing DNA, but some danger signals possess low molecular weight structures. It has been found that the PRR bind unit structures of PAMP, and that PAMP-binding involves several other humoral and cell membrane proteins, exemplified by the more or less simultaneous LPS recognition displayed by MD-2, CD-14 and TLR4 on the cell membrane. Also, the binding of beta-glucans has been shown to include several different cell membrane receptors. Several immunostimulants are commercially exploited in aquaculture as feed additives. This applies to beta-glucans, alginates and nucleotides. Despite their use as feed additives no targeted approach has been conducted to include PAMP as adjuvants in fish vaccines. Interestingly, most of the PAMP studied activate antigen-presenting cells together with naive T cells into dendritic cells and Th1 or Th2 cells [1]. In turn, this may activate Th1 and Th2 immune responses with production of Th1 or Th2 signature molecules such as IFN-gamma and IL-4, respectively [2-4]. This review will mainly focus on binding characteristics of beta-glucans, their effects on T helper cell differentiation, effects on functional levels, gene expression profiles and application of the commonly used beta-glucan in the aquaculture sector. In addition, beta-glucans show promises in shrimp aquaculture by inducing disease resistance, this review will also highlight the use and the effects of beta-glucans in experimental models. (c) 2008 Elsevier Ltd. All rights reserved.