Heat-labile enterotoxins as adjuvants or anti-inflammatory agents.
Escherichia coli and Vibrio cholerae produce structurally related AB5-type heat-labile enterotoxins, which are classified into two major types. The Type I subfamily includes cholera toxin and E. coli LT-I, whereas the Type II subfamily comprises LT-IIa and LT-IIb. In addition to their roles in microbial pathogenesis, the enterotoxins are widely and intensively studied for their exceptionally strong adjuvant and immunomodulatory activities, which are not necessarily dependent upon their abilities to elevate intracellular cAMP levels. Despite general structural similarities, these molecules, in intact or derivative form, display notable differences in their interactions with gangliosides or Toll-like receptors. This divergence results in differential immune response outcomes, the underlying mechanisms of which remain largely uncharacterized. Whereas the study of these molecules has been pivotal in understanding basic mechanisms of immune regulation, a formidable challenge is to dissociate toxicity from useful properties that can be exploited in vaccine development or for the treatment of autoimmune inflammatory diseases.
Liang
Shuang
S
University of Louisville School of Dentistry, Oral Health and Systemic Disease, Louisville, KY 40202, USA.
Hajishengallis
George
G
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D004768:Enterotoxins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D004768:Enterotoxins; D007155:Immunologic Factors
Immunol Cell Biol. 2007 Aug-Sep;85(6):490-4
17667933
J Immunol. 1997 Dec 1;159(11):5450-6
9548485
J Immunol. 2009 Mar 1;182(5):2978-85
19234193
J Immunol. 1999 Feb 15;162(4):2432-40
9973526
Infect Immun. 2001 Jul;69(7):4486-92
11401990
Immunity. 2004 Oct;21(4):467-76
15485625
J Autoimmun. 2002 Dec;19(4):223-32
12473243
Curr Opin Gastroenterol. 2008 Nov;24(6):713-9
19122521
J Infect Dis. 1996 Mar;173(3):627-35
8627026
J Exp Med. 2009 Jun 8;206(6):1227-35
19487420
J Leukoc Biol. 2004 May;75(5):756-63
14704372
Nat Rev Immunol. 2003 Feb;3(2):133-46
12563297
Vaccine. 2001 Mar 21;19(17-19):2534-41
11257389
Vaccine. 2003 Jun 1;21 Suppl 2:S89-95
12763689
J Immunol. 2000 Nov 15;165(10):5597-605
11067915
Arthritis Rheum. 2002 Jun;46(6):1671-82
12115200
J Immunol. 1999 Jun 15;162(12):7015-21
10358143
Infect Immun. 2004 Nov;72(11):6351-8
15501764
J Biol Chem. 1994 Jul 1;269(26):17359-62
8021233
Infect Immun. 1981 Sep;33(3):677-82
7026442
J Neuroimmunol. 1997 Nov;79(2):129-37
9394785
Vaccine. 1993;11(2):113-8
8382416
Nat Immunol. 2001 Aug;2(8):675-80
11477402
Vaccine. 2003 Mar 28;21(13-14):1445-54
12615441
Nat Med. 2005 Apr;11(4 Suppl):S45-53
15812489
J Exp Med. 2005 Jan 17;201(2):233-40
15657292
Vaccine. 1996 Feb;14(2):162-6
8852414
Proc Natl Acad Sci U S A. 2006 May 2;103(18):7048-53
16632602
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8536-41
11447291
Vaccine. 2009 Jul 9;27(32):4302-8
19450646
J Cell Biochem. 1991 Apr;45(4):327-34
2045425
J Immunol. 1995 Feb 1;154(3):1032-40
7822780
J Immunol. 2007 Apr 15;178(8):4811-9
17404262
Clin Immunol. 2000 Nov;97(2):130-9
11027453
Annu Rev Immunol. 2007;25:821-52
17201677
Nat Immunol. 2004 Oct;5(10):987-95
15454922
J Immunol. 1991 May 1;146(9):2908-14
1901890
Eur J Immunol. 2002 Nov;32(11):3216-24
12555667
Eur J Immunol. 1992 Sep;22(9):2277-81
1381311
Expert Rev Vaccines. 2007 Oct;6(5):821-34
17931161
J Exp Med. 2003 Dec 15;198(12):1951-7
14662908
Mol Microbiol. 1994 Oct;14(1):51-60
7830560
Infect Immun. 2000 Jan;68(1):281-7
10603399
Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7196-201
8692968
Annu Rev Immunol. 2006;24:353-89
16551253
Expert Rev Vaccines. 2007 Oct;6(5):673-84
17931149
Eur J Immunol. 2003 Jan;33(1):224-32
12594851
Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):226-30
8552610
Immunology. 1997 Aug;91(4):572-8
9378497
J Immunol. 1995 Nov 15;155(10):4621-9
7594461
Infect Immun. 2005 Mar;73(3):1343-9
15731031
J Biol Chem. 2007 Mar 9;282(10):7532-42
17227759
Gastroenterology. 1989 Nov;97(5):1186-92
2551764
J Dent Res. 2008 Sep;87(9):817-28
18719207
Microbes Infect. 2003 Nov;5(13):1241-7
14623020
Invest Ophthalmol Vis Sci. 2008 Sep;49(9):4008-17
18469197
Immunity. 1995 Mar;2(3):271-9
7697544
J Exp Med. 1990 Jul 1;172(1):95-103
2162906
Infect Immun. 2005 Mar;73(3):1330-42
15731030
J Biol Chem. 2003 Feb 21;278(8):5597-604
12493739
J Dent Res. 2005 Dec;84(12):1104-16
16304439
J Immunol. 2000 Nov 15;165(10):5750-9
11067933
J Immunol. 2003 Sep 1;171(5):2384-92
12928385
Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9
11413487
J Cell Sci. 2002 Jun 15;115(Pt 12):2603-11
12045230
Immunol Rev. 1999 Aug;170:197-222
10566152
Semin Immunol. 1997 Aug;9(4):235-40
9237929
J Immunol. 1997 Dec 1;159(11):5301-8
9548469
Infect Immun. 1995 Jun;63(6):2356-60
7768621
Infect Immun. 2005 May;73(5):2718-27
15845474
Vaccine. 2001 Oct 12;20(1-2):134-9
11567757
PLoS One. 2009;4(4):e5190
19360100
Structure. 1996 Jun 15;4(6):665-78
8805549
Vaccine. 1993 Sep;11(12):1179-84
8256498
Nat Immunol. 2005 Aug;6(8):777-84
16007092
Infect Immun. 1992 Dec;60(12):5057-64
1333448
Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):11960-5
11035810