| First Author | Watanabe S | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 4 | Pages | e60078 |
| PubMed ID | 23565187 | Mgi Jnum | J:199946 |
| Mgi Id | MGI:5506667 | Doi | 10.1371/journal.pone.0060078 |
| Citation | Watanabe S, et al. (2013) Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14. PLoS One 8(4):e60078 |
| abstractText | Lipopolysaccharide (LPS) is recognized by CD14 with Toll-like receptor 4 (TLR4), and initiates 2 major pathways of TLR4 signaling, the MyD88-dependent and TRIF-dependent signaling pathways. The MyD88-dependent pathway induces inflammatory responses such as the production of TNF-alpha, IL-6, and IL-12 via the activation of NFkappaB and MAPK. The TRIF-dependent pathway induces the production of type-I IFN, and RANTES via the activation of IRF-3 and NFkappaB, and is also important for the induction of adaptive immune responses. CD14 plays a critical role in initiating the TRIF-dependent signaling pathway response to LPS, to support the internalization of LPS via endocytosis. Here, we clearly demonstrate that intracellular delivery of LPS by LPS-formulated liposomes (LPS-liposomes) initiate only TRIF-dependent signaling via clathrin-mediated endocytosis, independent of CD14. In fact, LPS-liposomes do not induce the production of TNF-alpha and IL-6 but induce RANTES production in peritoneal macrophages. Additionally, LPS-liposomes could induce adaptive immune responses effectively in CD14-deficient mice. Collectively, our results strongly suggest that LPS-liposomes are useful as a TRIF-dependent signaling-based immune adjuvant without inducing unnecessary inflammation. |
