Inhibitory Siglec-sialic acid interactions in balancing immunological activation and tolerance during viral infections

Siglecs are a family of emerging glyco-immune checkpoints. Inhibiting them can enhance the functions of several types of immune cells, whereas engaging them can reduce hyper-inflammation and hyper-activation of immune functions. Siglec-sialoglycan interactions play an important role in modulating immunological functions during cancer, however, their roles in regulating immunological equilibrium during viral infections is less clear. In this review, we discuss the documented and potential roles of inhibitory Siglecs in balancing immune activation and tolerance during viral infections and consider how this balance could affect both the desired anti-viral immunological functions and the unwanted hyper- or chronic inflammation. Finally, we discuss the opportunities to target the Siglec immunological switches to reach an immunological balance during viral infections: inhibiting specific Siglec-sialoglycan interactions when maximum anti-viral immune responses are needed, or inducing other interactions when preventing excessive inflammation or reducing chronic immune activation are the goals. Copyright (C) 2022 The Author(s). Published by Elsevier B.V.

Automated summary

Siglecs are a family of emerging glyco-immune checkpoints that can enhance immune cell functions when inhibited and reduce hyper-inflammation when engaged. While their roles in modulating immunological functions during cancer are well-documented, their roles in regulating immunological equilibrium during viral infections are less clear. This review discusses the potential roles of inhibitory Siglecs in balancing immune activation and tolerance during viral infections and explores the opportunities to target Siglec immunological switches to achieve immunological balance.