Invariant natural killer T cells: boon or bane in immunity to intracellular bacterial infections?

Invariant natural killer T (iNKT) cells represent a specialized subset of innate lymphocytes that recognize lipid and glycolipid antigens presented to them by nonclassical MHC-I CD1d molecules and are able to rapidly secrete copious amounts of a variety of cytokines. iNKT cells possess the ability to modulate innate as well as adaptive immune responses against various pathogens. Intracellular bacteria are one of the most clinically significant human pathogens that effectively evade the immune system and cause a myriad of diseases of public health concern globally. Emerging evidence suggests that iNKT cells can confer immunity to intracellular bacteria but also inflict pathology in certain cases. We summarize the current knowledge on the contribution of iNKT cells in the host defense against intracellular bacterial infections, with a focus on the underlying mechanisms by which these cells induce protective or pathogenic reactions including the pathways of direct action (acting on infected cells) and indirect action (modulating dendritic, NK and T cells). The rational exploitation of iNKT cells for prophylactic and therapeutic purposes awaits a profound understanding of their functional biology.