Dynamics of NKT-Cell Responses to Chlamydial Infection

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.

Keywords: CD1d restriction; Chlamydia; NKT cells; dendritic cells.

Figure 1

Induction of anti-chlamydial T-cell responses by iNKT cells through DC modulation. During chlamydial infections, iNKT cells induce DC maturation through IFN-γ, CD40–CD40L binding, iTCR–Ag interaction, and cell-to-cell contact. Once matured, DCs induce enhanced production of IL-12 that skews Th1/Tc responses. Th1/Tc responses characterized by IFN-γ production lead to the clearance of intracellular Chlamydiae.