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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  ;  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 
 Nature Microbiology, Vol.2 : 16191, 2017-01 
Journal Title
 Nature Microbiology 
Issue Date
Animals ; Bacterial Infections/immunology* ; Bacterial Infections/pathology ; Bacterial Load ; Chemokines/secretion ; Humans ; Immunity, Innate* ; Immunologic Factors/administration & dosage ; Immunologic Factors/blood ; Immunologic Factors/secretion* ; Macrophages/immunology ; Mice ; Monocytes/immunology ; Phagocytosis ; Salmonella Infections, Animal ; Salmonella typhimurium/isolation & purification ; Sepsis/immunology ; Sepsis/pathology ; Survival Analysis ; Tryptophan-tRNA Ligase/administration & dosage ; Tryptophan-tRNA Ligase/blood ; Tryptophan-tRNA Ligase/secretion*
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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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Park, Kyung Hee(박경희) ORCID logo https://orcid.org/0000-0003-3605-5364
Park, Jung Won(박중원) ORCID logo https://orcid.org/0000-0003-0249-8749
Park, Hye Jung(박혜정) ORCID logo https://orcid.org/0000-0002-1862-1003
Lee, Jae Hyun(이재현) ORCID logo https://orcid.org/0000-0002-0760-0071
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