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Review
. 2020 Jan 4:2020:2045860.
doi: 10.1155/2020/2045860. eCollection 2020.

Toll-Like Receptors in Natural Killer Cells and Their Application for Immunotherapy

Ji-Yoon Noh  1 , Suk Ran Yoon  1   2 , Tae-Don Kim  1   2 , Inpyo Choi  1   2 , Haiyoung Jung  1
Affiliations
Review

Toll-Like Receptors in Natural Killer Cells and Their Application for Immunotherapy

Ji-Yoon Noh et al. J Immunol Res. .

Abstract

Innate immunity represents the first barrier for host defense against microbial infection. Toll-like receptors (TLRs) are the most well-defined PRRs with respect to PAMP recognition and induction of innate immune responses. They recognize pathogen-associated molecular patterns (PAMPs) and trigger innate immune responses by inducing inflammatory cytokines, chemokines, antigen-presenting molecules, and costimulatory molecules. TLRs are expressed either on the cell surface or within endosomes of innate immune cells. NK cells are one of the innate immune cells and also express TLRs to recognize or respond to PAMPs. TLRs in NK cells induce the innate immune responses against bacterial and viral infections via inducing NK cytotoxicity and cytokine production. In this review, we will discuss the expression and cellular function of TLRs in NK cells and also introduce some therapeutic applications of TLR agonists for NK cell-mediated immunotherapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PAMP recognition by TLRs and adaptor proteins to mediate cellular signaling pathways. TLR members can be divided into cell surface types (TLR1, 2, 4, 5, and 6) and endosome types (TLR3, 7, 8, and 9). TLRs form homo- or heterodimer and have their respective ligands to be activated. After ligand binding to TLRs, TLRs dimerize and undergo the conformational change to recruit downstream adaptor proteins including myeloid differentiation primary response gene 88 (MyD88), TIR domain-containing adaptor protein (TIRAP)/MyD88-adaptor-like (Mal), TIR domain-containing adaptor inducing IFN-β (TRIF)/TIR domain-containing adaptor molecule-1 (TICAM-1), and TRIF-related adaptor molecule (TRAM).
Figure 2
Figure 2
Overview of TLR-mediated signaling pathways. Activated TLRs trigger the association of adaptor proteins and activate their downstream molecules to induce the production of cytokines and cytotoxicity of NK cells.
Figure 3
Figure 3
Application of TLR agonists for NK cell-mediated therapy. NK cells are activated directly by TLR agonists through TLRs or indirectly by NK cell-activating cytokines released by dendritic cells (DCs) and macrophages (MΦ). NK cells also activate DCs and macrophages by secretion of IFN-γ and TNF-α.
See this image and copyright information in PMC

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