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

Yuki Kinjo,Masahiro Abe,Shogo Takatsuka,Yoshitsugu Miyazaki,Shun Kawakubo,Naoki Kitano,Keigo Ueno

doi:10.3389/fimmu.2018.01266

Yuki Kinjo, Masahiro Abe + Show 5 more

Open Access

https://doi.org/10.3389/fimmu.2018.01266

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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.

Highlights

Natural killer T (NKT) cells are innate-type lymphocytes that recognize glycolipid antigens presented by the major histocompatibility complex (MHC) class I-like molecule CD1d [1,2,3,4,5,6,7]
CD1d and can, activate invariant NKT (iNKT) cells [26]. iNKT cells have been shown to recognize a B. burgdorferi glycolipid presented by CD1d [27, 28], and the ensuing activation contributes to bacterial clearance and prevention of joint and heart inflammation [24, 25]. Consistent with these observations, mice deficient in iNKT cells or depleted of Kupffer cells exhibited bacterial dissemination to bladder, joints, and heart [26]. These results indicate that iNKT cells contribute to the immune response against B. burgdorferi during the early phase of infection by recognizing bacterial glycolipids presented by Kupffer cells in liver sinusoids, thereby preventing bacterial dissemination to other tissues
Numerous studies have demonstrated that CD1d-resticted iNKT cells contribute to immune responses against a broad spectrum of pathogenic microbes despite constituting only a small fraction of the leukocyte population

Summary

Introduction

Natural killer T (NKT) cells are innate-type lymphocytes that recognize glycolipid antigens presented by the MHC class I-like molecule CD1d [1,2,3,4,5,6,7]. INKT cells activated by glycolipid antigens produce cytokines and express CD40 ligand (CD40L), which stimulates the maturation of APCs, such as dendritic cells (DCs), leading to the augmentation of acquired immune responses [1,2,3,4,5,6]. Following infection by Aspergillus fumigatus, a major cause of invasive fungal infection in immunocompromised patients, iNKT cells produce IFNγ in response to recognition of endogenous antigens presented by CD1d, while APCs such as DCs release IL-12 in response to stimulation by β-glucan, resulting in the promotion of fungal clearance [16].

Results

Conclusion