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

Overview

Journal J Immunol Res

Publisher Wiley

Specialty Allergy & Immunology

Date 2020 May 8

PMID 32377528

Citations 42

Authors

Ji-Yoon Noh

Suk Ran Yoon

Tae-Don Kim

Inpyo Choi

Haiyoung Jung

Affiliations

Soon will be listed here.

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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References

Schmidt M, Hagner N, Marco A, Konig-Merediz S, Schroff M, Wittig B . Design and Structural Requirements of the Potent and Safe TLR-9 Agonistic Immunomodulator MGN1703. Nucleic Acid Ther. 2015; 25(3):130-40. PMC: 4440985. DOI: 10.1089/nat.2015.0533. View

Vaknin I, Blinder L, Wang L, Gazit R, Shapira E, Genina O . A common pathway mediated through Toll-like receptors leads to T- and natural killer-cell immunosuppression. Blood. 2007; 111(3):1437-47. DOI: 10.1182/blood-2007-07-100404. View

Fitzgerald K, Palsson-McDermott E, Bowie A, Jefferies C, Mansell A, Brady G . Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature. 2001; 413(6851):78-83. DOI: 10.1038/35092578. View

Anguille S, Van Acker H, Van den Bergh J, Willemen Y, Goossens H, Van Tendeloo V . Interleukin-15 Dendritic Cells Harness NK Cell Cytotoxic Effector Function in a Contact- and IL-15-Dependent Manner. PLoS One. 2015; 10(5):e0123340. PMC: 4423923. DOI: 10.1371/journal.pone.0123340. View

Marcenaro E, Carlomagno S, Pesce S, Moretta A, Sivori S . Bridging innate NK cell functions with adaptive immunity. Adv Exp Med Biol. 2011; 780:45-55. DOI: 10.1007/978-1-4419-5632-3_5. View

Hallek M, Fischer K, Fingerle-Rowson G, Fink A, Busch R, Mayer J . Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010; 376(9747):1164-74. DOI: 10.1016/S0140-6736(10)61381-5. View

Coban C, Ishii K, Kawai T, Hemmi H, Sato S, Uematsu S . Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. J Exp Med. 2005; 201(1):19-25. PMC: 2212757. DOI: 10.1084/jem.20041836. View

Burns K, Martinon F, Esslinger C, Pahl H, Schneider P, Bodmer J . MyD88, an adapter protein involved in interleukin-1 signaling. J Biol Chem. 1998; 273(20):12203-9. DOI: 10.1074/jbc.273.20.12203. View

Schmidt S, Tramsen L, Rais B, Ullrich E, Lehrnbecher T . Natural killer cells as a therapeutic tool for infectious diseases - current status and future perspectives. Oncotarget. 2018; 9(29):20891-20907. PMC: 5945539. DOI: 10.18632/oncotarget.25058. View

10.

Ferlazzo G, Pack M, Thomas D, Paludan C, Schmid D, Strowig T . Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs. Proc Natl Acad Sci U S A. 2004; 101(47):16606-11. PMC: 534504. DOI: 10.1073/pnas.0407522101. View

11.

Marcenaro E, Ferranti B, Falco M, Moretta L, Moretta A . Human NK cells directly recognize Mycobacterium bovis via TLR2 and acquire the ability to kill monocyte-derived DC. Int Immunol. 2008; 20(9):1155-67. DOI: 10.1093/intimm/dxn073. View

12.

Patel H, Shaw S, Shi-Wen X, Abraham D, Baker D, Tsui J . Toll-like receptors in ischaemia and its potential role in the pathophysiology of muscle damage in critical limb ischaemia. Cardiol Res Pract. 2012; 2012:121237. PMC: 3290818. DOI: 10.1155/2012/121237. View

13.

Dunne A, ONeill L . The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci STKE. 2003; 2003(171):re3. DOI: 10.1126/stke.2003.171.re3. View

14.

Krug A, French A, Barchet W, Fischer J, Dzionek A, Pingel J . TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity. 2004; 21(1):107-19. DOI: 10.1016/j.immuni.2004.06.007. View

15.

Jin M, Kim S, Heo J, Lee M, Kim H, Paik S . Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell. 2007; 130(6):1071-82. DOI: 10.1016/j.cell.2007.09.008. View

16.

Herberman R, Nunn M, HOLDEN H, LAVRIN D . Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. II. Characterization of effector cells. Int J Cancer. 1975; 16(2):230-9. DOI: 10.1002/ijc.2910160205. View

17.

Janssens S, Beyaert R . Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members. Mol Cell. 2003; 11(2):293-302. DOI: 10.1016/s1097-2765(03)00053-4. View

18.

Baselga J, Perez E, Pienkowski T, Bell R . Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancer. Oncologist. 2006; 11 Suppl 1:4-12. DOI: 10.1634/theoncologist.11-90001-4. View

19.

Vivier E, Raulet D, Moretta A, Caligiuri M, Zitvogel L, Lanier L . Innate or adaptive immunity? The example of natural killer cells. Science. 2011; 331(6013):44-9. PMC: 3089969. DOI: 10.1126/science.1198687. View

20.

Bell J, Askins J, Hall P, Davies D, Segal D . The dsRNA binding site of human Toll-like receptor 3. Proc Natl Acad Sci U S A. 2006; 103(23):8792-7. PMC: 1482657. DOI: 10.1073/pnas.0603245103. View