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

Young Ha Ahn, Sunyoung Park, Jeong June Choi, Bo Kyung Park, Kyung Hee Rhee, Eunjoo Kang, Soyeon Ahn, Chul Ho Lee, Jong Soo Lee, Kyung Soo Inn, Mi La Cho, Sung Hwan Park, Kyunghee Park, Hae Jung Park, Jae Hyun Lee, Jung Won Park, Nam Hoon Kwon, Hyunbo Shim, Byung Woo Han, Pilhan KimJoo Youn Lee, Youngho Jeon, Jin Won Huh, Mirim Jin, Sunghoon Kim

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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.

Original languageEnglish
Article number16191
JournalNature microbiology
StatePublished - 17 Oct 2016

Bibliographical note

Funding Information:
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 and Future Planning (MSIP) of Korea.

Publisher Copyright:
© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.


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