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