The hybrid between the ABC domains of synapsin and the B subunit of Escherichia coli heat-labile toxin ameliorates experimental autoimmune encephalomyelitis

被引:4
|
作者
Bibolini, Mario J. [1 ]
Julia Scerbo, M. [1 ]
Peinetti, Nahuel [1 ]
Roth, German A. [1 ]
Monferran, Clara G. [1 ]
机构
[1] Natl Univ Cordoba, Fac Ciencias Quim, Ctr Invest Quim Biol Cordoba CIQUIBIC, UNC CONICET,Dept Quim Biol, RA-5016 Cordoba, Argentina
关键词
Autoimmunity; Experimental autoimmune encephalomyelitis; Immunomodulation; Escherichia coli heat-labile enterotoxin; Synapsin; MYELIN BASIC-PROTEIN; CHOLERA-TOXIN; CRYSTAL-STRUCTURE; ENTEROTOXIN; INDUCTION; BINDING; CELLS; IMMUNOGENICITY; SPECIFICITY; MACROPHAGES;
D O I
10.1016/j.cellimm.2012.11.012
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The B subunit of Escherichia coli heat-labile enterotoxin (LTB) acts as efficient mucosal carrier for conjugated antigens. We expressed two heterologous proteins using E. coli as a host: a hybrid consisting of LTB and the A, B and C domain of synapsin (LTBABC) and the separated ABC peptide of this synaptic protein. Refolded LTBABC and LTB bound to the GM1 receptor and internalized into CHO-K1(GM1+) cells. LTBABC showed enhanced solubility and cell binding ability respect to the former hybrid LTBSC. Several oral doses of LTBABC were administered to rats with experimental autoimmune encephalomyelitis (EAE) from induction to the acute stage of the disease. This treatment decreased disease severity, delayed type hypersensitivity reaction and lymph node cell proliferation stimulated by myelin basic protein. Amelioration of EAE was also associated with modulation of the Th1/Th2 cytokine ratio, increased TGF-beta secretion in mesenteric lymph nodes as well as expansion of CD4(+)CD25(+)Foxp3(+) regulatory T cell population. These results indicate that the fusion protein LTBABC is suitable for further exploration of its therapeutic effect on EAE development. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:50 / 60
页数:11
相关论文
共 50 条
  • [31] PROTECTIVE EFFECT OF IMMUNIZATION OF RATS WITH HOLOTOXIN OR B-SUBUNIT OF ESCHERICHIA-COLI HEAT-LABILE ENTERO-TOXIN
    KLIPSTEIN, FA
    ENGERT, RF
    INFECTION AND IMMUNITY, 1981, 31 (01) : 144 - 150
  • [32] Oral immunization with a lettuce-derived Escherichia coli heat-labile toxin B subunit induces neutralizing antibodies in mice
    Martinez-Gonzalez, Luzmila
    Rosales-Mendoza, Sergio
    Soria-Guerra, Ruth Elena
    Moreno-Fierros, Leticia
    Lopez-Revilla, Ruben
    Korban, Schuyler S.
    Guevara-Arauza, Juan C.
    Alpuche-Solis, Angel Gabriel
    PLANT CELL TISSUE AND ORGAN CULTURE, 2011, 107 (03) : 441 - 449
  • [33] Intranuclear delivery of an antiviral peptide mediated by the B subunit of Escherichia coli heat-labile enterotoxin
    Loregian, A
    Papini, E
    Satin, B
    Marsden, HS
    Hirst, TR
    Palù, G
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (09) : 5221 - 5226
  • [34] Expression of the B subunit of Escherichia coli heat-labile enterotoxin as a fusion protein in transgenic tomato
    Walmsley, AM
    Alvarez, ML
    Jin, Y
    Kirk, DD
    Lee, SM
    Pinkhasov, J
    Rigano, MM
    Arntzen, CJ
    Mason, HS
    PLANT CELL REPORTS, 2003, 21 (10) : 1020 - 1026
  • [35] Induction of regulatory T cell responses by the B subunit of the Escherichia coli heat-labile enterotoxin
    Donaldson, D. S.
    Tong, K. K.
    William, N. A.
    IMMUNOLOGY, 2008, 125 : 132 - 132
  • [36] Expression of Functional Pentameric Heat-Labile Enterotoxin B Subunit of Escherichia coli in Saccharomyces cerevisiae
    Lim, Jung-Gu
    Kim, Jung-Ae
    Chung, Hea-Jong
    Kim, Tae-Geum
    Kim, Jung-Mi
    Lee, Kyung-Ryul
    Park, Seung-Moon
    Yang, Moon-Sik
    Kim, Dae-Hyuk
    JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY, 2009, 19 (05) : 502 - 510
  • [37] Immunogenicity of the B monomer of Escherichia coli heat-labile toxin expressed on the surface of Streptococcus gordonii
    Ricci, S
    Medaglini, D
    Rush, CM
    Marcello, A
    Peppoloni, S
    Manganelli, R
    Palu, G
    Pozzi, G
    INFECTION AND IMMUNITY, 2000, 68 (02) : 760 - 766
  • [38] A COMPLETELY SYNTHETIC TOXOID VACCINE CONTAINING ESCHERICHIA-COLI HEAT-STABLE TOXIN AND ANTIGENIC DETERMINANTS OF THE HEAT-LABILE TOXIN-B SUBUNIT
    HOUGHTEN, RA
    ENGERT, RF
    OSTRESH, JM
    HOFFMAN, SR
    KLIPSTEIN, FA
    INFECTION AND IMMUNITY, 1985, 48 (03) : 735 - 740
  • [39] Expression of the B subunit of Escherichia coli heat-labile enterotoxin as a fusion protein in transgenic tomato
    A. M. Walmsley
    M. L. Alvarez
    Y. Jin
    D. D. Kirk
    S. M. Lee
    J. Pinkhasov
    M. M. Rigano
    C. J. Arntzen
    H. S. Mason
    Plant Cell Reports, 2003, 21 : 1020 - 1026
  • [40] PROTECTION IN RABBITS IMMUNIZED WITH A VACCINE OF ESCHERICHIA-COLI HEAT-STABLE TOXIN CROSS-LINKED TO THE HEAT-LABILE TOXIN-B SUBUNIT
    KLIPSTEIN, FA
    ENGERT, RF
    HOUGHTEN, RA
    INFECTION AND IMMUNITY, 1983, 40 (03) : 888 - 893