Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling

被引:459
作者
Gavin, Amanda L.
Hoebe, Kasper
Duong, Bao
Ota, Takayuki
Martin, Christopher
Beutler, Bruce
Nemazee, David
机构
[1] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Kellogg Sch Sci & Technol, Doctoral Program Chem & Biol Sci, La Jolla, CA 92037 USA
关键词
D O I
10.1126/science.1135299
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Innate immune signals mediated by Toll-like receptors (TLRs) have been thought to contribute considerably to the antibody-enhancing effects of vaccine adjuvants. However, we report here that mice deficient in the critical signaling components for TLR mount robust antibody responses to T cell-dependent antigen given in four typical adjuvants: alum, Freund's complete adjuvant, Freund's incomplete adjuvant, and monophosphoryl-lipid A/trehalose dicorynomycolate adjuvant. We conclude that TLR signaling does not account for the action of classical adjuvants and does not fully explain the action of a strong adjuvant containing a TLR ligand. This may have important implications in the use and development of vaccine adjuvants.
引用
收藏
页码:1936 / 1938
页数:3
相关论文
共 17 条
  • [1] ANDERSSON J, 1972, TRANSPLANT REV-DENMA, V11, P131
  • [2] Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large
    Beutler, Bruce
    Jiang, Zhengfan
    Georgel, Philippe
    Crozat, Karine
    Croker, Ben
    Rutschmann, Sophie
    Du, Xin
    Hoebe, Kasper
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2006, 24 : 353 - 389
  • [3] REGULATION BY INTERFERON-ALPHA OF IMMUNOGLOBULIN ISOTYPE SELECTION AND LYMPHOKINE PRODUCTION IN MICE
    FINKELMAN, FD
    SVETIC, A
    GRESSER, I
    SNAPPER, C
    HOLMES, J
    TROTTA, PP
    KATONA, IM
    GAUSE, WC
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 174 (05) : 1179 - 1188
  • [4] Identification of Lps2 as a key transducer of MyD88-independent TIR signalling
    Hoebe, K
    Du, X
    Georgel, P
    Janssen, E
    Tabeta, K
    Kim, SO
    Goode, J
    Lin, P
    Mann, N
    Mudd, S
    Crozat, K
    Sovath, S
    Han, J
    Beutler, B
    [J]. NATURE, 2003, 424 (6950) : 743 - 748
  • [5] Efficient T cell activation via a Toll-interleukin 1 Receptor-independent pathway
    Janssen, Edith
    Tabeta, Koichi
    Barnes, Michael J.
    Rutschmann, Sophie
    McBride, Sara
    Bahjat, Keith S.
    Schoenberger, Stephen P.
    Theofilopoulos, Argyrios N.
    Beutler, Bruce
    Hoebe, Kasper
    [J]. IMMUNITY, 2006, 24 (06) : 787 - 799
  • [6] Endotoxin can induce MyD88-deficient dendritic cells to support Th2 cell differentiation
    Kaisho, T
    Hoshino, K
    Iwabe, T
    Takeuchi, O
    Yasui, T
    Akira, S
    [J]. INTERNATIONAL IMMUNOLOGY, 2002, 14 (07) : 695 - 700
  • [7] RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement
    Lau, CM
    Broughton, C
    Tabor, AS
    Akira, S
    Flavell, RA
    Mamula, MJ
    Christensen, SR
    Shlomchik, MJ
    Viglianti, GA
    Rifkin, IR
    Marshak-Rothstein, A
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 202 (09) : 1171 - 1177
  • [8] Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors
    Leadbetter, EA
    Rifkin, IR
    Hohlbaum, AM
    Beaudette, BC
    Shlomchik, MJ
    Marshak-Rothstein, A
    [J]. NATURE, 2002, 416 (6881) : 603 - 607
  • [9] Toll-like receptors and antibody responses
    Nemazee, D
    Gavin, A
    Hoebe, K
    Beutler, B
    [J]. NATURE, 2006, 441 (7091) : E4 - E4
  • [10] Toll-like receptors: balancing host resistance with immune tolerance
    Pasare, C
    Medzhitov, R
    [J]. CURRENT OPINION IN IMMUNOLOGY, 2003, 15 (06) : 677 - 682