Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14.
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-α, IL-6, and IL-12 vi...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23565187/?tool=EBI |
| _version_ | 1828957576662876160 |
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| author | Sachiko Watanabe Yoshio Kumazawa Joe Inoue |
| author_facet | Sachiko Watanabe Yoshio Kumazawa Joe Inoue |
| author_sort | Sachiko Watanabe |
| collection | DOAJ |
| description | 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-α, IL-6, and IL-12 via the activation of NFκB and MAPK. The TRIF-dependent pathway induces the production of type-I IFN, and RANTES via the activation of IRF-3 and NFκB, 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-α 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. |
| first_indexed | 2024-12-14T08:32:40Z |
| format | Article |
| id | doaj.art-6721fa6ac81842ce943a8f7ef884b4d7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T08:32:40Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6721fa6ac81842ce943a8f7ef884b4d72022-12-21T23:09:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6007810.1371/journal.pone.0060078Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14.Sachiko WatanabeYoshio KumazawaJoe InoueLipopolysaccharide (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-α, IL-6, and IL-12 via the activation of NFκB and MAPK. The TRIF-dependent pathway induces the production of type-I IFN, and RANTES via the activation of IRF-3 and NFκB, 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-α 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23565187/?tool=EBI |
| spellingShingle | Sachiko Watanabe Yoshio Kumazawa Joe Inoue Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14. PLoS ONE |
| title | Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14. |
| title_full | Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14. |
| title_fullStr | Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14. |
| title_full_unstemmed | Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14. |
| title_short | Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14. |
| title_sort | liposomal lipopolysaccharide initiates trif dependent signaling pathway independent of cd14 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23565187/?tool=EBI |
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