β‐Glucan Internalization

Following oral β‐glucan administration, PRRs expressed on the cell surface of macrophages from the microfolds of Peyer's patches (M cells) bind and internalize β‐glucan upon arrival in the small intestinal lumen, as seen by fluorescence microscopy in murine spleen and bone marrow tissues. Once internalized, β‐glucan‐containing innate immune cells travel to the different organs of the immune system where smaller and more soluble β‐1,3‐glucan fragments are released over several days to interact with and modulate the functional capacity of the innate immune response. Whether β‐glucan‐containing macrophages are transported to the lymphoid organs via lymphatic or systemic circulation in humans is still unclear,[although rat and mouse models show intact β‐glucan being shuttled from the gastrointestinal tract to the different immune organs through the systemic circulation. Subsequent fragmentation into smaller biologically active β‐1,3‐glucan particles occurs on days 3–5 after ingestion, β‐1,3‐glucan fragments are released extracellularly from days 5–10 and diminish after 14–21 days.β‐glucan receptors include dectin‐1,CR3,lactosylceramide,TLR 2, 4, and 6,cluster of differentiation 36 (CD36),and scavenger receptors like CD5.Dectin‐1 and CR3 have been extensively characterized for their direct interaction with β‐glucans and their ability to subsequently alter the immune response, whereas the other receptors mainly become involved later on during the intracellular signaling cascade. While CR3 is highly expressed on neutrophils, monocytes, natural killer (NK) cells, and to a lesser extent on macrophages, dectin‐1 is mainly expressed on macrophages, followed by granulocytes, and is absent from NK cells. Consequently, the main receptor mediating yeast phagocytosis in macrophages is dectin‐1, but CR3 is the predominant receptor in granulocytes.