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 Kim; Joo Youn Lee; Youngho Jeon; Jin Won Huh; Mirim Jin; Sunghoon Kim

doi:10.1038/nmicrobiol.2016.191

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

Department of Life Science

Research output: Contribution to journal › Article › peer-review

66 Scopus citations

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.

Original language	English
Article number	16191
Journal	Nature microbiology
Volume	2
DOIs	https://doi.org/10.1038/nmicrobiol.2016.191
State	Published - 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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Ahn, Y. H., Park, S., Choi, J. J., Park, B. K., Rhee, K. H., Kang, E., Ahn, S., Lee, C. H., Lee, J. S., Inn, K. S., Cho, M. L., Park, S. H., Park, K., Park, H. J., Lee, J. H., Park, J. W., Kwon, N. H., Shim, H., Han, B. W., ... Kim, S. (2016). Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection. Nature microbiology, 2, Article 16191. https://doi.org/10.1038/nmicrobiol.2016.191

@article{a0897490cc5747c69fbfa13306647b72,

title = "Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection",

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.",

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

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: {\textcopyright} 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.",

year = "2016",

month = oct,

day = "17",

doi = "10.1038/nmicrobiol.2016.191",

language = "English",

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journal = "Nature microbiology",

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Ahn, YH, Park, S, Choi, JJ, Park, BK, Rhee, KH, Kang, E, Ahn, S, Lee, CH, Lee, JS, Inn, KS, Cho, ML, Park, SH, Park, K, Park, HJ, Lee, JH, Park, JW, Kwon, NH, Shim, H, Han, BW, Kim, P, Lee, JY, Jeon, Y, Huh, JW, Jin, M & Kim, S 2016, 'Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection', Nature microbiology, vol. 2, 16191. https://doi.org/10.1038/nmicrobiol.2016.191

TY - JOUR

T1 - Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection

AU - Ahn, Young Ha

AU - Park, Sunyoung

AU - Choi, Jeong June

AU - Park, Bo Kyung

AU - Rhee, Kyung Hee

AU - Kang, Eunjoo

AU - Ahn, Soyeon

AU - Lee, Chul Ho

AU - Lee, Jong Soo

AU - Inn, Kyung Soo

AU - Cho, Mi La

AU - Park, Sung Hwan

AU - Park, Kyunghee

AU - Park, Hae Jung

AU - Lee, Jae Hyun

AU - Park, Jung Won

AU - Kwon, Nam Hoon

AU - Shim, Hyunbo

AU - Han, Byung Woo

AU - Kim, Pilhan

AU - Lee, Joo Youn

AU - Jeon, Youngho

AU - Huh, Jin Won

AU - Jin, Mirim

AU - Kim, Sunghoon

N1 - 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.

PY - 2016/10/17

Y1 - 2016/10/17

N2 - 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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Secreted tryptophanyl-tRNA synthetase as a primary defence system against infection

Abstract

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