Effects of Invariant NKT Cells on Parasite Infections and Hygiene Hypothesis.

Jun-Qi Yang,Ram Raj Singh,Yonghua Zhou

doi:10.1155/2016/2395645

Abstract

Invariant natural killer T (iNKT) cells are unique subset of innate-like T cells recognizing glycolipids. iNKT cells can rapidly produce copious amounts of cytokines upon antigen stimulation and exert potent immunomodulatory activities for a wide variety of immune responses and diseases. We have revealed the regulatory effect of iNKT cells on autoimmunity with a serial of publications. On the other hand, the role of iNKT cells in parasitic infections, especially in recently attractive topic “hygiene hypothesis,” has not been clearly defined yet. Bacterial and parasitic cell wall is a cellular structure highly enriched in a variety of glycolipids and lipoproteins, some of which may serve as natural ligands of iNKT cells. In this review, we mainly summarized the recent findings on the roles and underlying mechanisms of iNKT cells in parasite infections and their cross-talk with Th1, Th2, Th17, Treg, and innate lymphoid cells. In most cases, iNKT cells exert regulatory or direct cytotoxic roles to protect hosts against parasite infections. We put particular emphasis as well on the identification of the natural ligands from parasites and the involvement of iNKT cells in the hygiene hypothesis.

Highlights

Natural killer T (NKT) cells are recently discovered innatelike subset of lymphocytes expressing both NK and T cell markers
Type I NKT cells are called invariant NKT, expressing exclusively limited T cell receptor α (TCRα) and TCRβ receptors, that is, Vα14-Jα18 predominately paired with Vβ8.2, Vβ7, or Vβ2 in mice and Vα24-Jα18 paired with Vβ11 in human [2, 3]. iNKT cells secrete a wide array of cytokines and chemokines immediately upon activation through TCR engagement by glycolipids. iNKT cells exert their regulatory and cytotoxic activities through direct contact, granzyme B, or FasLinduced mechanisms [4,5,6]
INKT cells have been further classified into NKT1, NKT2, and NKT17 lineages based on their cytokine profiles and distinct transcription factors, T-Bet, Gata-3, and Rorγt, as conventional T helper 1 (Th1), Th2, and Th17 cells [8, 9]

Summary

Introduction

Natural killer T (NKT) cells are recently discovered innatelike subset of lymphocytes expressing both NK and T cell markers. Type I NKT cells are called invariant NKT (iNKT), expressing exclusively limited T cell receptor α (TCRα) and TCRβ receptors, that is, Vα14-Jα18 predominately paired with Vβ8.2, Vβ7, or Vβ2 in mice and Vα24-Jα18 paired with Vβ11 in human [2, 3]. INKT cells exert both regulator and effector cell function and bridge the innate and adaptive immune responses [7]. Type II NKT cells, which are called non-iNKT or variant NKT (vNKT) cells, express more diverse TCRα and TCRβ receptors [10]. A hallmark of iNKT cells is their capacity to rapidly produce copious amounts of cytokines and chemokines upon TCR stimulation, which endows these cells with potent immunomodulatory activities for a wide variety of immune responses and diseases (Figure 1). We summarize the roles of iNKT cells in parasitic infections, with particular emphasis on the involvement of iNKT cells in the hygiene hypothesis and underlying mechanisms

NKT Cells in Parasitic Infections

Contribution of NKT Cells to Hygiene Hypothesis

Conclusions