Functions of CD1d-Restricted Invariant Natural Killer T Cells in Antimicrobial Immunity and Potential Applications for Infection Control

CD1d-restricted invariant natural killer T ( NKT) cells are innate-type lymphocytes that express a T-cell receptor (TCR) containing an invariant α chain encoded by the gene in mice and gene in humans. These NKT cells recognize endogenous, microbial, and synthetic glycolipid antigens presented by the major histocompatibility complex (MHC) class I-like molecule CD1d. Upon TCR stimulation by glycolipid antigens, NKT cells rapidly produce large amounts of cytokines, including interferon-γ (IFNγ) and interleukin-4 (IL-4). Activated NKT cells contribute to host protection against a broad spectrum of microbial pathogens, and glycolipid-mediated stimulation of NKT cells ameliorates many microbial infections by augmenting innate and acquired immunity. In some cases, however, antigen-activated NKT cells exacerbate microbial infections by promoting pathogenic inflammation. Therefore, it is important to identify appropriate microbial targets for the application of NKT cell activation as a treatment or vaccine adjuvant. Many studies have found that NKT cell activation induces potent adjuvant activities promoting protective vaccine effects. In this review, we summarize the functions of CD1d-restricted NKT cells in immune responses against microbial pathogens and describe the potential applications of glycolipid-mediated NKT cell activation for preventing and controlling microbial infections.