Dynamics of NKT-Cell Responses to Chlamydial Infection.

Sudhanshu Shekhar,Xi Yang,Antony George Joyee

doi:10.3389/fimmu.2015.00233

Abstract

Natural killer T (NKT) cells have gained great attention owing to their critical functional roles in immunity to various pathogens. In this review, we provide an overview of the current knowledge on the role of NKT cells in host defense against and pathogenesis due to Chlamydia, which is an intracellular bacterial pathogen that poses a threat to the public health worldwide. Accumulating evidence has demonstrated that NKT cells, particularly invariant NKT (iNKT) cells, play a crucial role in host defense against chlamydial infections, especially in C. pneumoniae infection. iNKT cells can promote type-1 protective responses to C. pneumoniae by inducing enhanced production of IL-12 by dendritic cells (DCs), in particular CD8α+ DCs, which promote the differentiation of naive T cells into protective IFN-γ-producing Th1/Tc1 type CD4+/CD8+ T cells. This iNKT-cell-mediated modulation of DC function is largely dependent upon CD40–CD40L interaction, IFN-γ production, and cell-to-cell contact. In addition, iNKT cells modulate the function of natural killer cells. NKT cells may be also involved in the pathogenesis of some chlamydial diseases by inducing different patterns of cytokine production. A better understanding of NKT-cell biology will enable us to rationally design prophylactic and therapeutic tools to combat infectious diseases.

Highlights

Natural killer T (NKT) cells represent a unique population of innate lymphocytes that express the natural killer (NK)- and T-cell markers, such as NK1.1 and αβ T-cell receptor (TCR) [1]
Adoptive transfer of dendritic cell (DC) isolated from the spleens of C. pneumoniae-infected Jα18-KO, in contrast to the WT, mice promoted infection and pathology in naïve recipient mice upon challenge with chlamydial infection [62], suggesting that invariant NKT (iNKT) cells are crucial for DCs to confer protective T helper cell (Th1)/Tc1 immunity
Invariant NKT cells play an important role in immunity to chlamydial infections

Summary

Introduction

Natural killer T (NKT) cells represent a unique population of innate lymphocytes that express the natural killer (NK)- and T-cell markers, such as NK1.1 and αβ T-cell receptor (TCR) [1]. INKT cells possess the invariant αβ TCR (iTCR) that recognizes glycolipid and lipid antigens presented to them by CD1d molecules. Type II NKT cells do not express the iTCR and are reactive to sulfatides [1]. Because of their distinct immunologic characteristics and crucial functions in host immune responses to different pathogens, NKT cells have gained much attention in recent years [3]. We describe how iNKT cells bridge innate and adaptive immunity by modulating the function of dendritic cells (DCs) during chlamydial infection. NKT cells in immunity to chlamydial infection present a rational basis for developing effective prophylactics and therapeutics against infectious diseases

Chlamydial Infections and Their Pathophysiology

Activation of iNKT Cells

Bridging Innate and Adaptive Immunity

Findings

Conclusion and Future Directions