The phagocytic capacity and immunological potency of human dendritic cells is improved by α2,6‐sialic acid deficiency

Summary Dendritic cells ( DC s) play an essential role in immunity against bacteria by phagocytosis and by eliciting adaptive immune responses. Previously, we demonstrated that human monocyte‐derived DC s ( MDDC s) express a high content of cell surface α2,6‐sialylated glycans. However, the relative role of these sialylated structures in phagocytosis of bacteria has not been reported. Here, we show that treatment with a sialidase significantly improved the capacity of both immature and mature MDDC s to phagocytose E scherichia coli . Desialylated MDDC s had a significantly more mature phenotype, with higher expression of MHC molecules and interleukin ( IL )‐12, tumour necrosis factor‐α, IL ‐6 and IL ‐10 cytokines, and nuclear factor‐κB activation. T lymphocytes primed by desialylated MDDC s expressed more interferon‐γ when compared with priming by sialylated MDDC s. Improved phagocytosis required E . coli sialic acids, indicating a mechanism of host–pathogen interaction dependent on sialic acid moieties. The DC s harvested from mice deficient in the ST 6 G al.1 sialyltransferase showed improved phagocytosis capacity, demonstrating that the observed sialidase effect was a result of the removal of α2,6‐sialic acid. The phagocytosis of different pathogenic E . coli isolates was also enhanced by sialidase, which suggests that modifications on MDDC sialic acids may be considered in the development of MDDC ‐based antibacterial therapies. Physiologically, our findings shed new light on mechanisms that modulate the function of both immature and mature MDDC s, in the context of host–bacteria interaction. Hence, with particular relevance to DC ‐based therapies, the engineering of α2,6‐sialic acid cell surface is a novel possibility to fine tune DC phagocytosis and immunological potency.