Modulation of immune responses through direct activation of Toll-like receptors to T cells

Abstract

Toll-like receptors (TLRs), which are a family of pattern recognition receptors (PRRs), are involved critically in the generation and regulation of innate immunity as well as initiation of subsequent adaptive immune responses. However, recent research results showed that different subsets of T cells express certain types of TLRs during development and activation stages. Importantly, TLRs participate in the direct regulation of adaptive immune response, possibly as co-stimulatory molecules. In this review we summarize recent studies about the novel regulation of TLRs on the homeostasis and immunity of different T cell subtypes including CD4+CD25+T regulatory cells (Treg) and interleukin (IL)-17-producing CD4+T cells (T helper type 17). The direct involvement of TLRs in T cell-mediated immunity prompted us to reconsider the role of TLRs in the occurrence of autoimmune diseases, infectious diseases and graft rejection. The important effects of TLRs in T cell-intrinsic components also prompt us to explore novel vaccine adjuvants for modifying desired immune responses in an efficient way.

Fig. 1

Modulation of innate and adaptive immunity through Toll-like receptor (TLR) signalling. A brief summary for the role of TLRs in triggering innate and adaptive immunity via multiple approaches.

Fig. 2

Effects of Toll-like receptor (TLR) agonist proposed to modulate directly the function of naturally occurring CD4⁺CD25⁺ T regulatory (T_reg) cells upon direct interaction of the TLR ligand with the TLRs expressing on/in CD4⁺CD25⁺ T cells. Pretreatment of CD4⁺CD25⁺ T_reg cells with TLR-2, -4 and -5 agonists enhance the immunosuppressive activity; in contrast, TLR-1/2, -8 and -9 agonists abrogate the suppressive activity of CD4⁺CD25⁺ T_reg cells. Teff: effector T cells.

Fig. 3

Antigen-presenting cells (APCs) [macrophages and/or dendritic cells (DCs)] to induce T helper type 17 (Th17) or CD4⁺CD25⁺ T regulatory (T_reg) responses through TLR signalling. Signalling via TLR-3, -4, -7 or -8 involved in triggering of APCs promotes induction of proinflammatory cytokines including interleukin (IL)-6, IL-1, IL-21 and IL-23 and thus mediate the Th17 response, and also inhibits the CD4⁺CD25⁺ T_reg cell activity.