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Nat Microbiol. 2016 Oct 17;2:16191. doi: 10.1038/nmicrobiol.2016.191.

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

Author information

1
College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
2
College of Korean Medicine, Daejeon University, Daejeon 34520, Republic of Korea.
3
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
4
Medicinal Bioconvergence Research Center, Seoul National University, Suwon 16229, Republic of Korea.
5
Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
6
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon 34113, Republic of Korea.
7
College of Veterinary Medicine, Chungnam National University, Daejeon 34134, Republic of Korea.
8
Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
9
Divison of Rheumatology, Department of Internal Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea.
10
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 06591, Republic of Korea.
11
Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
12
Institute of Allergy, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
13
Departments of Bioinspired Science and Life Science, Ewha Womans University, Seoul 03760, Republic of Korea.
14
Korea Chemical Bank, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.
15
College of Pharmacy, Korea University, Sejong 30019, Republic of Korea.
16
Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.

Abstract

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.

PMID:
27748732
DOI:
10.1038/nmicrobiol.2016.191
[Indexed for MEDLINE]

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