Chitin oligomers directly promote lymphoid innate and adaptive immune cell activation

Abstract

BackgroundChitin is a highly abundant N-acetyl-glucosamine (GlcNAc) polysaccharide which has been linked to immune responses in the context of fungal infections and allergic asthma, especially T helper 2 (Th2) immune responses. Unfortunately, due to the frequent use of crude chitin preparations of unknown purity and degree of polymerization there is still great uncertainty how chitin activates different parts of the human immune system. ObjectiveWe recently identified chitin oligomers of six GlcNAc units as the smallest immunologically active chitin motif and the innate immune receptor TLR2 as primary chitin sensor on human and murine myeloid cells, but the response of lymphoid cells to oligomeric chitin has not been investigated and was addressed here. MethodsFlow cytometric analysis of primary human immune cells upon stimulation with oligomeric chitin. For detailed Methods, please see the Methods section in this articles Online Repository at www.jacionline.org. ResultHere we report that chitin oligomers also activate immune responses by both primary lymphoid innate and adaptive immune cells: Notably, chitin oligomers activated Natural Killer (NK) cells and B lymphocytes. Moreover, the maturation of dendritic cells enabled CD8 T cell recall responses. ConclusionsOur results suggest that chitin oligomers not only trigger immediate innate responses in limited range of myeloid cells but exert critical activities across the entire human immune system. Key messagesChitin oligomers are microbe-associated molecular patterns involved in TLR2-dependent fungal recognition by myeloid immune cells. Here we show that lymphoid cells, most notably Natural Killer (NK) cells and B cells, are activated by oligomeric chitin. Oligomeric chitin also promotes antigen-presenting cell (APC) maturation and CD8 T cell recall responses. Capsule summaryOligomeric chitin is a novel microbe-associated molecular patterns involved in TLR2-dependent fungal recognition by myeloid innate immune cells. Here we show that lymphoid innate and adaptive immune responses are also promoted by oligomeric chitin.