Liposomal Lipopolysaccharide Initiates TRIF-Dependent Signaling Pathway Independent of CD14.

• Watanabe, Sachiko

• Kumazawa, Yoshio

• 井上, 浄

• Yoshihiko Hoshino

  editor

抄録

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.

収録刊行物

• PloS one

  PloS one 8 (4), e60078-, 2013-04-02

  Public Library of Science

キーワード

• Multidisciplinary

詳細情報

• CRID: 1050001335767352704
• NII論文ID: 120005244422
• ISSN: 19326203
• DOI: 10.1371/journal.pone.0060078
• HANDLE: 2433/173356
• Web Site: http://dx.plos.org/10.1371/journal.pone.0060078
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
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