title: Heat-labile enterotoxins as adjuvants or anti-inflammatory agents.
abstract: 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.
authors.affiliation: University of Louisville School of Dentistry, Oral Health and Systemic Disease, Louisville, KY 40202, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.forename: George
authors.initials: G
authors.lastname: Hajishengallis
mesh_terms: 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*
chemical_list: D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D004768:Enterotoxins; D007155:Immunologic Factors
references.citation: Immunol Cell Biol. 2007 Aug-Sep;85(6):490-4
references.pmid: 17667933
references.citation: J Immunol. 1997 Dec 1;159(11):5450-6
references.pmid: 9548485
references.citation: J Immunol. 2009 Mar 1;182(5):2978-85
references.pmid: 19234193
references.citation: J Immunol. 1999 Feb 15;162(4):2432-40
references.pmid: 9973526
references.citation: Infect Immun. 2001 Jul;69(7):4486-92
references.pmid: 11401990
references.citation: Immunity. 2004 Oct;21(4):467-76
references.pmid: 15485625
references.citation: J Autoimmun. 2002 Dec;19(4):223-32
references.pmid: 12473243
references.citation: Curr Opin Gastroenterol. 2008 Nov;24(6):713-9
references.pmid: 19122521
references.citation: J Infect Dis. 1996 Mar;173(3):627-35
references.pmid: 8627026
references.citation: J Exp Med. 2009 Jun 8;206(6):1227-35
references.pmid: 19487420
references.citation: J Leukoc Biol. 2004 May;75(5):756-63
references.pmid: 14704372
references.citation: Nat Rev Immunol. 2003 Feb;3(2):133-46
references.pmid: 12563297
references.citation: Vaccine. 2001 Mar 21;19(17-19):2534-41
references.pmid: 11257389
references.citation: Vaccine. 2003 Jun 1;21 Suppl 2:S89-95
references.pmid: 12763689
references.citation: J Immunol. 2000 Nov 15;165(10):5597-605
references.pmid: 11067915
references.citation: Arthritis Rheum. 2002 Jun;46(6):1671-82
references.pmid: 12115200
references.citation: J Immunol. 1999 Jun 15;162(12):7015-21
references.pmid: 10358143
references.citation: Infect Immun. 2004 Nov;72(11):6351-8
references.pmid: 15501764
references.citation: J Biol Chem. 1994 Jul 1;269(26):17359-62
references.pmid: 8021233
references.citation: Infect Immun. 1981 Sep;33(3):677-82
references.pmid: 7026442
references.citation: J Neuroimmunol. 1997 Nov;79(2):129-37
references.pmid: 9394785
references.citation: Vaccine. 1993;11(2):113-8
references.pmid: 8382416
references.citation: Nat Immunol. 2001 Aug;2(8):675-80
references.pmid: 11477402
references.citation: Vaccine. 2003 Mar 28;21(13-14):1445-54
references.pmid: 12615441
references.citation: Nat Med. 2005 Apr;11(4 Suppl):S45-53
references.pmid: 15812489
references.citation: J Exp Med. 2005 Jan 17;201(2):233-40
references.pmid: 15657292
references.citation: Vaccine. 1996 Feb;14(2):162-6
references.pmid: 8852414
references.citation: Proc Natl Acad Sci U S A. 2006 May 2;103(18):7048-53
references.pmid: 16632602
references.citation: Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8536-41
references.pmid: 11447291
references.citation: Vaccine. 2009 Jul 9;27(32):4302-8
references.pmid: 19450646
references.citation: J Cell Biochem. 1991 Apr;45(4):327-34
references.pmid: 2045425
references.citation: J Immunol. 1995 Feb 1;154(3):1032-40
references.pmid: 7822780
references.citation: J Immunol. 2007 Apr 15;178(8):4811-9
references.pmid: 17404262
references.citation: Clin Immunol. 2000 Nov;97(2):130-9
references.pmid: 11027453
references.citation: Annu Rev Immunol. 2007;25:821-52
references.pmid: 17201677
references.citation: Nat Immunol. 2004 Oct;5(10):987-95
references.pmid: 15454922
references.citation: J Immunol. 1991 May 1;146(9):2908-14
references.pmid: 1901890
references.citation: Eur J Immunol. 2002 Nov;32(11):3216-24
references.pmid: 12555667
references.citation: Eur J Immunol. 1992 Sep;22(9):2277-81
references.pmid: 1381311
references.citation: Expert Rev Vaccines. 2007 Oct;6(5):821-34
references.pmid: 17931161
references.citation: J Exp Med. 2003 Dec 15;198(12):1951-7
references.pmid: 14662908
references.citation: Mol Microbiol. 1994 Oct;14(1):51-60
references.pmid: 7830560
references.citation: Infect Immun. 2000 Jan;68(1):281-7
references.pmid: 10603399
references.citation: Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7196-201
references.pmid: 8692968
references.citation: Annu Rev Immunol. 2006;24:353-89
references.pmid: 16551253
references.citation: Expert Rev Vaccines. 2007 Oct;6(5):673-84
references.pmid: 17931149
references.citation: Eur J Immunol. 2003 Jan;33(1):224-32
references.pmid: 12594851
references.citation: Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):226-30
references.pmid: 8552610
references.citation: Immunology. 1997 Aug;91(4):572-8
references.pmid: 9378497
references.citation: J Immunol. 1995 Nov 15;155(10):4621-9
references.pmid: 7594461
references.citation: Infect Immun. 2005 Mar;73(3):1343-9
references.pmid: 15731031
references.citation: J Biol Chem. 2007 Mar 9;282(10):7532-42
references.pmid: 17227759
references.citation: Gastroenterology. 1989 Nov;97(5):1186-92
references.pmid: 2551764
references.citation: J Dent Res. 2008 Sep;87(9):817-28
references.pmid: 18719207
references.citation: Microbes Infect. 2003 Nov;5(13):1241-7
references.pmid: 14623020
references.citation: Invest Ophthalmol Vis Sci. 2008 Sep;49(9):4008-17
references.pmid: 18469197
references.citation: Immunity. 1995 Mar;2(3):271-9
references.pmid: 7697544
references.citation: J Exp Med. 1990 Jul 1;172(1):95-103
references.pmid: 2162906
references.citation: Infect Immun. 2005 Mar;73(3):1330-42
references.pmid: 15731030
references.citation: J Biol Chem. 2003 Feb 21;278(8):5597-604
references.pmid: 12493739
references.citation: J Dent Res. 2005 Dec;84(12):1104-16
references.pmid: 16304439
references.citation: J Immunol. 2000 Nov 15;165(10):5750-9
references.pmid: 11067933
references.citation: J Immunol. 2003 Sep 1;171(5):2384-92
references.pmid: 12928385
references.citation: Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9
references.pmid: 11413487
references.citation: J Cell Sci. 2002 Jun 15;115(Pt 12):2603-11
references.pmid: 12045230
references.citation: Immunol Rev. 1999 Aug;170:197-222
references.pmid: 10566152
references.citation: Semin Immunol. 1997 Aug;9(4):235-40
references.pmid: 9237929
references.citation: J Immunol. 1997 Dec 1;159(11):5301-8
references.pmid: 9548469
references.citation: Infect Immun. 1995 Jun;63(6):2356-60
references.pmid: 7768621
references.citation: Infect Immun. 2005 May;73(5):2718-27
references.pmid: 15845474
references.citation: Vaccine. 2001 Oct 12;20(1-2):134-9
references.pmid: 11567757
references.citation: PLoS One. 2009;4(4):e5190
references.pmid: 19360100
references.citation: Structure. 1996 Jun 15;4(6):665-78
references.pmid: 8805549
references.citation: Vaccine. 1993 Sep;11(12):1179-84
references.pmid: 8256498
references.citation: Nat Immunol. 2005 Aug;6(8):777-84
references.pmid: 16007092
references.citation: Infect Immun. 1992 Dec;60(12):5057-64
references.pmid: 1333448
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):11960-5
references.pmid: 11035810