How invariant natural killer T cells respond to infection by recognizing microbial or endogenous lipid antigens

Invariant natural killer T (iNKT) cells have evolved to recognize CD1d-presented lipid antigens and are known to play important roles during infection with bacterial, viral, protozoan, and fungal pathogens. The limited antigen specificity and reactivity to self- and foreign antigens distinguish iNKT cells from MHC-restricted T cells and bear similarity to innate-like lymphocytes, such as NK cells, gammadelta T cells, MZB and B1-B cells. This review summarizes how direct recognition of microbial lipids or synergistic stimulation by self-lipids and pro-inflammatory cytokines results in activation of these innate-like iNKT cell during infection. iNKT cell activation in the absence of foreign antigen recognition is unique for cells bearing TCRs and underscores that not only the function but also the activation mechanism of iNKT cells is innate-like, and distinct from adaptive T cells. The different pathways of activation endow iNKT cells with the ability to respond rapidly to a wide variety of infectious agents and to contribute effectively to the early immune response during infection.