Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection

  • Nature Microbiology 2, Article number: 16191 (2016)
  • doi:10.1038/nmicrobiol.2016.191
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The N-terminal truncated form of a protein synthesis enzyme, tryptophanyl-tRNA synthetase (mini-WRS), is secreted as an angiostatic ligand. However, the secretion and function of the full-length WRS (FL-WRS) remain unknown. Here, we report that the FL-WRS, but not mini-WRS, is rapidly secreted upon pathogen infection to prime innate immunity. Blood levels of FL-WRS were increased in sepsis patients, but not in those with sterile inflammation. FL-WRS was secreted from monocytes and directly bound to macrophages via a toll-like receptor 4 (TLR4)–myeloid differentiation factor 2 (MD2) complex to induce phagocytosis and chemokine production. Administration of FL-WRS into Salmonella typhimurium-infected mice reduced the levels of bacteria and improved mouse survival, whereas its titration with the specific antibody aggravated the infection. The N-terminal 154-amino-acid eukaryote-specific peptide of WRS was sufficient to recapitulate FL-WRS activity and its interaction mode with TLR4–MD2 is now suggested. Based on these results, secretion of FL-WRS appears to work as a primary defence system against infection, acting before full activation of innate immunity.

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This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2010-0012505), Bio-Synergy/research Project (2014M3A9C4066465) and Global Frontier Project grants nos. NRF-M3A6A4-2010-0029785 and 2015M3A6A4065732 of the National Research Foundation funded by the Ministry of Science, ICT & Future Planning (MSIP) of Korea.

Author information

Author notes

    • Young Ha Ahn
    •  & Sunyoung Park

    These authors contributed equally to this work.


  1. College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea

    • Young Ha Ahn
    • , Joo-Youn Lee
    •  & Sunghoon Kim
  2. College of Korean Medicine, Daejeon University, Daejeon 34520, Republic of Korea

    • Sunyoung Park
    • , Jeong June Choi
    • , Bo-Kyung Park
    •  & Mirim Jin
  3. Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea

    • Kyung Hee Rhee
    •  & Byung Woo Han
  4. Medicinal Bioconvergence Research Center, Seoul National University, Suwon 16229, Republic of Korea

    • Eunjoo Kang
    • , Nam Hoon Kwon
    •  & Sunghoon Kim
  5. Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea

    • Soyeon Ahn
    •  & Pilhan Kim
  6. Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon 34113, Republic of Korea

    • Chul-Ho Lee
  7. College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Republic of Korea

    • Jong Soo Lee
  8. Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea

    • Kyung-Soo Inn
  9. Divison of Rheumatology, Department of Internal Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea

    • Mi-La Cho
  10. The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 06591, Republic of Korea

    • Sung-Hwan Park
  11. Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

    • Kyunghee Park
    • , Hye Jung Park
    • , Jae-Hyun Lee
    •  & Jung-Won Park
  12. Institute of Allergy, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

    • Kyunghee Park
    • , Hye Jung Park
    • , Jae-Hyun Lee
    •  & Jung-Won Park
  13. Departments of Bioinspired Science and Life Science, Ewha Womans University, Seoul 03760, Republic of Korea

    • Hyunbo Shim
  14. Korea Chemical Bank, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea

    • Joo-Youn Lee
  15. College of Pharmacy, Korea University, Sejong 30019, Republic of Korea

    • Youngho Jeon
  16. Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea

    • Jin Won Huh


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Co-first authors Y.H.A. and S.P. performed the experiments and analysed the data. J.J.C., B.-K.P., K.H.R., E.K., S.A., K.-S.I., N.H.K., H.S., B.W.H., P.K., J.-Y.L. and Y.J. performed experiments. C.-H.L. and J.S.L. provided knockout animals. M.-L.C., S.-H.P., K.P., H.J.P., J.-H.L., J.-W.P. and J.W.H. provided sera and discussed clinical data. M.J. and S.K. designed the experiments, supervised the research and wrote the paper. All authors approved the final manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Mirim Jin or Sunghoon Kim.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    Supplementary Figures 1–9, Supplementary Tables 1 and 2, legends for Supplementary Videos 1–6


  1. 1.

    Supplementary Video 1

    Infiltration of neutrophil and monocyte/macraophage 30 min after PBS injection.

  2. 2.

    Supplementary Video 2

    Infiltration of neutrophil and monocyte/macraophage 4 hr after PBS injection.

  3. 3.

    Supplementary Video 3

    Infiltration of neutrophil and monocyte/macraophage 30 min after FL-WRS injection.

  4. 4.

    Supplementary Video 4

    Infiltration of neutrophil and monocyte/macraophage 4 hr after FL-WRS injection.

  5. 5.

    Supplementary Video 5

    Infiltration of neutrophil and monocyte/macraophage 30 min after mini-WRS 23 injection.

  6. 6.

    Supplementary Video 6

    Infiltration of neutrophil and monocyte/macraophage 4 hr after mini-WRS injection.