全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...
PLOS ONE  2013 

Intracellular Delivery of Lipopolysaccharide Induces Effective Th1-Immune Responses Independent of IL-12

DOI: 10.1371/journal.pone.0068671

Full-Text   Cite this paper   Add to My Lib

Abstract:

Lipopolysaccharide (LPS) is responsible for many of the inflammatory responses and pathogenic effects of Gram-negative bacteria, however, it also induces protective immune responses. LPS induces the production of inflammatory cytokines such as TNF-α, IL-6, and IL-12 from dendritic cells (DCs) and macrophages. It is thought that IL-12 is required for one of the protective immune responses induced by LPS, the T helper 1 (Th1)-immune response, which include the production of IFN-γ from Th1cells and IgG2c class switching. Here, we clearly demonstrate that intracellular delivery of LPS by LPS-formulated liposomes (LPS-liposomes) does not induce the production of inflammatory cytokines from DCs, but enhances Th1-immune responses via type-I IFNs, independent of IL-12. Collectively, our results strongly suggest that LPS-liposomes can effectively induce Th1-immune responses without inducing unnecessary inflammation, and may be useful as an immune adjuvant to induce protective immunity.

References

[1]  Beutler B (2002) TLR4 as the mammalian endotoxin sensor. Curr Top Microbiol Immunol 270: 109–120.
[2]  Miller SI, Ernst RK, Bader MW (2005) LPS TLR4 and infectious disease diversity. Nat Rev Microbiol 3: 36–46.
[3]  Miyake K (2004) Innate recognition of lipopolysaccharide by Toll-like receptor 4-MD-2. Trends Microbiol 12: 186–192.
[4]  Yamamoto M, Akira S (2009) Lipid A receptor TLR4-mediated signaling pathways. Adv Exp Med Biol 667: 59–68.
[5]  Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11: 373–384.
[6]  Kawai T, Akira S (2011) Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34: 637–650.
[7]  Jiang Z, Georgel P, Du X, Shamel L, Sovath S, et al. (2005) CD14 is required for MyD88-independent LPS signaling. Nat Immunol 6: 565–570.
[8]  Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, et al. (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301: 640–643.
[9]  Yamamoto M, Sato S, Hemmi H, Uematsu S, Hoshino K, et al. (2003) TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat Immunol 4: 1144–1150.
[10]  Kagan JC, Su T, Horng T, Chow A, Akira S, et al. (2008) TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β. Nat Immunol 9: 361–368.
[11]  Fitzgerald KA, Rowe DC, Barnes BJ, Caffrey DR, Visintin A, et al. (2003) LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF. J Exp Med 198: 1043–1055.
[12]  Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O’Garra A, et al. (1993) Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 260: 547–549.
[13]  Magram J, Connaughton SE, Warrier RR, Carvajal DM, Wu CY, et al. (1996) IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses. Immunity 4: 471–481.
[14]  Su SB, Silver PB, Grajewski RS, Agarwal RK, Tang J, et al. (2005) Essential role of the MyD88 pathway, but nonessential roles of TLRs 2, 4, and 9, in the adjuvant effect promoting Th1-mediated autoimmunity. J Immunol 175: 6303–6310.
[15]  Kaisho T, Hoshino K, Iwabe T, Takeuchi O, Yasui T, et al. (2002) Endotoxin can induce MyD88-deficient dendritic cells to support T(h)2 cell differentiation. Int Immunol 14: 695–700.
[16]  Puneet P, McGrath MA, Tay HK, Al-Riyami L, Rzepecka J, et al. (2011) The helminth product ES-62 protects against septic shock via Toll-like receptor 4-dependent autophagosomal degradation of the adaptor MyD88. Nat Immunol. 12: 344–351.
[17]  Mata-Haro V, Cekic C, Martin M, Chilton PM, Casella CR, et al. (2007) The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4. Science 316: 1628–1632.
[18]  Watanabe S, Kumazawa Y, Inoue J (2013) Liposomal Lipopolysaccharide Initiates TRIF-Dependent Signaling Pathway Independent of CD14. PLoS One 8: e60078.
[19]  Inoue J, Ideue R, Takahashi D, Kubota M, Kumazawa Y (2009) Liposomal glycosphingolipids activate natural killer T cell-mediated immune responses through the endosomal pathway. J Control Release 133: 18–23.
[20]  Inoue J, Aramaki Y (2007) Toll-like receptor-9 expression induced by tape-stripping triggers on effective immune response with CpG-oligodeoxynucleotides. Vaccine 25: 1007–1013.
[21]  Inoue J, Aramaki Y (2007) Suppression of skin lesions by transdermal application of CpG-oligodeoxynucleotides in NC/Nga mice, a model of human atopic dermatitis. J Immunol 178: 584–591.
[22]  Inoue J, Yotsumoto S, Sakamoto T, Tsuchiya S, Aramaki Y (2005) Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in mice. J Control Release 108: 294–305.
[23]  Inoue J, Aramaki Y (2007) Cyclooxygenase-2 inhibition promotes enhancement of antitumor responses by transcutaneous vaccination with cytosine-phosphate-guanosine-oligodeoxyn?ucleotidesand model tumor antigen. J Invest Dermatol 127: 614–621.
[24]  Inoue J, Yotsumoto S, Sakamoto T, Tsuchiya S, Aramaki Y (2005) Changes in immune responses to antigen applied to tape-stripped skin with CpG-oligodeoxynucleotide in NC/Nga mice. Pharm Res 22: 1627–1633.
[25]  Kaisho T, Takeuchi O, Kawai T, Hoshino K, Akira S (2001) Endotoxin-induced maturation of MyD88-deficient dendritic cells. J Immunol 166: 5688–5694.
[26]  Petrovsky N, Aguilar JC (2004) Vaccine adjuvants: current state and future trends. Immunol Cell Biol 82: 488–496.
[27]  ten Brinke A, van Schijndel G, Visser R, de Gruijl TD, Zwaginga JJ, et al. (2010) Monophosphoryl lipid A plus IFNgamma maturation of dendritic cells induces antigen-specific CD8+ cytotoxic T cells with high cytolytic potential. Cancer Immunol Immunother 59: 1185–1195.
[28]  Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, et al. (2003) Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature 424: 516–523.
[29]  Mu?oz-Fontela C, Macip S, Martínez-Sobrido L, Brown L, Ashour J, et al. (2008) Transcriptional role of p53 in interferon-mediated antiviral immunity. J Exp Med 205: 1929–1938.
[30]  Schoggins JW, Rice CM (2011) Interferon-stimulated genes and their antiviral effector functions. Curr Opin Virol 1: 519–525.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133