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

Abstract

CD1d-restricted invariant natural killer T (iNKT) cells are innate-type lymphocytes that express a T-cell receptor (TCR) containing an invariant α chain encoded by the Vα14 gene in mice and Vα24 gene in humans. These iNKT 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, iNKT cells rapidly produce large amounts of cytokines, including interferon-γ (IFNγ) and interleukin-4 (IL-4). Activated iNKT cells contribute to host protection against a broad spectrum of microbial pathogens, and glycolipid-mediated stimulation of iNKT cells ameliorates many microbial infections by augmenting innate and acquired immunity. In some cases, however, antigen-activated iNKT cells exacerbate microbial infections by promoting pathogenic inflammation. Therefore, it is important to identify appropriate microbial targets for the application of iNKT cell activation as a treatment or vaccine adjuvant. Many studies have found that iNKT cell activation induces potent adjuvant activities promoting protective vaccine effects. In this review, we summarize the functions of CD1d-restricted iNKT cells in immune responses against microbial pathogens and describe the potential applications of glycolipid-mediated iNKT cell activation for preventing and controlling microbial infections.

Antileishmanial Effects of Synthetic Eh PIb Analogs Derived from the Entamoeba histolytica Lipopeptidephosphoglycan

“…Second, uptake of the glycolipid leads to processing and loading onto CD1d molecules in the late endosomes of APCs. Subsequent presentation to invariant NKT cells, which express a semi-invariant ␣ T-cell receptor (␣TCR) paired with a limited repertoire of ␣TCR chains, elicits a strong immune response that leads to functions that are crucial for the control of several infectious diseases, including leishmaniasis (18,(24)(25)(26). This unique, dual mode of immune activation makes EhLPPG highly attractive for further development as an immunotherapeutic drug.…”

Host Immune Response and Novel Diagnostic Approach to NTM Infections

“…Natural killer T cells (NKT cells) are CD1-restricted T cells that possess semi-invariant T cell receptors. NKT cells recognize lipid antigens (e.g., MA, LAM, PIM, glucose monomycolate, and GroMN, a member of the CD1 family [54,55]) and can produce several cytokines immediately after activation [56]. NKT cells might play roles in modulating immune response after NTM infection, as well as Mtb infection [57].…”

Integrated multivariate analysis of transcriptomic data reveals immunological mechanisms in mice afterLeishmania infantuminfection

“…When the infection occurs, the chemotaxis of NKT cells is promoted by the production of CXCL9: iNKT cells produce cytokines, including interferon-γ (IFN-γ), interleukin-4 (IL-4), and IL-17A, that stimulate innate immune responses such as neutrophil recruitment (5). CCL3, CCL2 and CXCL10 are initially secreted in the liver, possibly by infected KC (6); this generates the initial recruitment of monocytes and neutrophils, which are critical for effective control of parasite growth.…”