Contribution of dectin-1 and granulocyte macrophage-colony stimulating factor (GM-CSF) to immunomodulating actions of beta-glucan.

beta-Glucans are major cell wall structural components in fungi. As they are not found in animals, these carbohydrates are considered to be classic pathogen-associated molecular patterns (PAMPs), and are recognized by the innate immune system. Although their immunomodulating activities have been shown to be associated with the recognition of some fungi, and with their medicinal properties in the field of cancer immunotherapy, it is still unclear how beta-glucans mediate their effects. Recent studies have started to shed some light on their cellular receptors, such as dectin-1, and their molecular mechanisms of action. We have extensively investigated the response of leukocytes to beta-glucan, focusing on cytokine induction by SCG, which is a major 6-branched 1,3-beta-d-glucan in Sparassis crispa Fr. There is a strain difference in the reactivity of mice to SCG, and DBA/1 and DBA/2 mice are highly sensitive strains. In the process of research on cytokine induction by SCG in DBA/2 mice, we found that GM-CSF plays a key biological role in this activity. Cytokine induction by SCG was completely abolished in dendritic cells from dectin-1 knockout mice. On the other hand, controlling the level of endogenous GM-CSF production and/or dectin-1 expression could regulate the reactivity to beta-glucan. These results indicate that the key factors in the responsiveness to beta-glucan are GM-CSF production and dectin-1 expression. In this review, we describe how the key molecules related to the expression of the immunomodulating activities of beta-glucan were identified, and how the response to beta-glucan is controlled.