Abstract
One of the key features of the immune system is its extraordinary capacity to discriminate between self and non-self and to respond accordingly. Several molecular interactions allow the induction of acquired immune responses when a foreign antigen is recognized, while others regulate the resolution of inflammation, or the induction of tolerance to self-antigens. Post-translational signatures, such as glycans that are part of proteins (glycoproteins) and lipids (glycolipids) of host cells or pathogens, are increasingly appreciated as key molecules in regulating immunity vs. tolerance. Glycans are sensed by glycan binding receptors expressed on immune cells, such as C-type lectin receptors (CLRs) and Sialic acid binding immunoglobulin type lectins (Siglecs), that respond to specific glycan signatures by triggering tolerogenic or immunogenic signaling pathways. Glycan signatures present on healthy tissue, inflamed and malignant tissue or pathogens provide signals for “self” or “non-self” recognition. In this review we will focus on sialic acids that serve as “self” molecular pattern ligands for Siglecs. We will emphasize on the function of Siglec-expressing mononuclear phagocytes as sensors for sialic acids in tissue homeostasis and describe how the sialic acid-Siglec axis is exploited by tumors and pathogens for the induction of immune tolerance. Furthermore, we highlight how the sialic acid-Siglec axis can be utilized for clinical applications to induce or inhibit immune tolerance.
Highlights
The human mononuclear phagocyte network consists of monocytes, different subsets of macrophages (MQ) and Dendritic cells (DCs) depending on their origin and tissue micro-environment
The last decade researchers identified the enormous potential of the sialic acid—Siglec axis to induce wanted or unwanted immune tolerance in cancer, allergies or auto-immune diseases
Both Siglec targeting antibodies, sialic acid mimetics, or glycan modifying agents can be used to interfere in this process and open new area’s in the design of novel therapies for cancer, allergy and auto-immune diseases
Summary
The human mononuclear phagocyte network consists of monocytes, different subsets of macrophages (MQ) and Dendritic cells (DCs) depending on their origin and tissue micro-environment. Both pathogens and tumor cells use enhanced expression of sialic acids as a mechanism to modify the immune system in their favor, illustrating that the sialic acid-Siglec axis is a key regulator in infection and cancer. An illustration of a trans interaction is α2,3 linked sialic acids expressed by lung epithelium under inflammatory conditions and Siglecs present on neutrophils [37, 38] (Figure 1C).
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