Cabral MG, Silva Z, Ligeiro D, Seixas E, Crespo H, Carrascal MA, Silva M, Piteira AR, Paixão P, Lau JT, Videira PA. (2012) The phagocytic capacity and immunological potency of human dendritic cells is improved by α2,6-sialic acid deficiency. Immunology. 138(3):235-245. PMID: 23113614; PMCID: PMC3573277
Dendritic cells (DCs) play an essential role in immunity against bacteria by phagocytosing and eliciting adaptive immune responses. Previously, we demonstrated that human monocyte derived DCs (MDDCs) express a high content of cell surface α2,6-sialylated glycans. However, the relative role of these sialylated structures in bacteria phagocytosis has not been reported. Here, we showed that treatment with a sialidase significantly improved the capacity of both immature and mature MDDCs to phagocytose Escherichia coli. Desialylated MDDCs had a significantly more mature phenotype, with higher expression of major histocompatibility complex 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 MDDCs expressed more interferon-γ when compared with priming by sialylated MDDCs. Improved phagocytosis required E. coli sialic acids, indicating a mechanism of host-pathogen interaction dependent of sialic acid moieties. DCs harvested from mice deficient in the ST6Gal.1 sialyltransferase (Siat1-null) showed improved phagocytosis capacity, demonstrating that the observed sialidase effect was due to 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 MDDCs, in the context of host-bacteria interaction. Thus, 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 © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.
Link to journal: http://www.jimmunol.org/