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...
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2013
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oai:doaj.org-article:6721fa6ac81842ce943a8f7ef884b4d72021-11-18T07:51:04ZLiposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14.1932-620310.1371/journal.pone.0060078https://doaj.org/article/6721fa6ac81842ce943a8f7ef884b4d72013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23565187/?tool=EBIhttps://doaj.org/toc/1932-6203Lipopolysaccharide (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.Sachiko WatanabeYoshio KumazawaJoe InouePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e60078 (2013) |
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Medicine R Science Q Sachiko Watanabe Yoshio Kumazawa Joe Inoue Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14. |
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. |
format |
article |
author |
Sachiko Watanabe Yoshio Kumazawa Joe Inoue |
author_facet |
Sachiko Watanabe Yoshio Kumazawa Joe Inoue |
author_sort |
Sachiko Watanabe |
title |
Liposomal lipopolysaccharide initiates TRIF-dependent signaling pathway independent of CD14. |
title_short |
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_sort |
liposomal lipopolysaccharide initiates trif-dependent signaling pathway independent of cd14. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doaj.org/article/6721fa6ac81842ce943a8f7ef884b4d7 |
work_keys_str_mv |
AT sachikowatanabe liposomallipopolysaccharideinitiatestrifdependentsignalingpathwayindependentofcd14 AT yoshiokumazawa liposomallipopolysaccharideinitiatestrifdependentsignalingpathwayindependentofcd14 AT joeinoue liposomallipopolysaccharideinitiatestrifdependentsignalingpathwayindependentofcd14 |
_version_ |
1718422856693448704 |