CD1d-iNKT Axis in Infectious Diseases: Lessons Learned From the Past

CD1d is an antigen-presenting molecule that presents lipid or glycolipid antigens to iNKT cells, a distinct subset of T lymphocytes characterised by their innate-like properties and restricted use of V_α, J_α and V_β segments. The CD1d-iNKT axis represents an interesting aspect of the immune system with significant potential for therapeutic interventions against infectious diseases. Upon recognition of lipid antigens, iNKT cells initiate rapid and potent immune responses, releasing a diverse array of cytokines such as IL-4, IL-13, IFN-γ etc. that profoundly influence immune reactions against various pathogens, including bacteria and parasites, bridging innate and adaptive immunity. We identify and describe the key features of lipidic antigens and their derivatives that determine the nature of their antigenicity. Furthermore, modulating CD1d-driven iNKT cell responses by an array of lipid and glycolipid antigens holds promise as adjunctive therapy to existing antimicrobial treatments. Understanding the complexities of the CD1d-iNKT axis and exploiting its therapeutic potential in the case of infectious diseases could lead to innovative immunotherapeutic strategies, ushering in a new era of immunotherapy against pathogenic insults.