Secreted Tryptophanyl-tRNA Synthetase as a Primary Defense 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, Hye 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

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 typhimuriuminfected 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.

Article Site: https://www.nature.com/articles/nmicrobiol2016191

Original Document: https://www.nature.com/articles/nmicrobiol2016191.pdf

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