Poly-γ-glutamic acid (γ-PGA) is an anionic polypeptide secreted by Bacillus sp. that has been shown to activate immune cells through interactions with toll-like receptor 4 (TLR4). However, its ability to induce the type I interferon (IFN) response has not yet been characterized. Here, we demonstrate that γ-PGA induces type I IFN signaling pathway via the TLR4 signaling pathway. The induction required both myeloid differentiation factor 2 (MD2) and the pattern-recognition receptor CD14, which are two TLR4-associated accessory proteins. The γ-PGA with high molecular weights (2000 and 5000kDa) was able to activate the subsequent signals through TLR4/MD2 to result in dimerization of IRF-3, a transcription factor required for IFN gene expression, leading to increases in mRNA levels of the type I IFN-response genes, 2'-5' OAS and ISG56. Moreover, γ-PGA (2000kDa) displayed an antiviral activity against SARS coronavirus and hepatitis C virus. Our results identify high-molecular weight γ-PGA as a TLR4 ligand and demonstrate that γ-PGA requires both CD14 and MD2 for the activation of type I IFN responses. Our results suggest that the microbial biopolymer γ-PGA may have therapeutic potential against a broad range of viruses sensitive to type I IFNs.
|Number of pages||9|
|Publication status||Published - 2013 Dec|
Bibliographical noteFunding Information:
This work was supported by a grant from the National Research Foundation of Korea (NRF-2012-0008693 ) and in part by the Technology Innovation Program (MKE 10035159) funded by the Ministry of Knowledge Economy (MKE, Korea) and by grants from the National Research Foundation of Korea funded by the Korean Government (MSIP) (NRF 2009-0092959 , 2012-047807 , and 2012-0008693 ).
All Science Journal Classification (ASJC) codes
- Ceramics and Composites
- Mechanics of Materials