Dermal enhancement: bacterial products on intact skin induce and augment organ-specific autoimmune disease.
The skin is both an essential barrier for host defense and an important organ of immunity. In this study, we show that the application of cholera toxin to intact mouse skin induces and enhances autoimmune diseases affecting organs at distant anatomic sites, whereas its administration by the mucosal route has been reported to have the opposite effect. First, the CNS autoantigen myelin oligodendrocyte glycoprotein 35-55, when applied repeatedly with cholera toxin to the intact skin of healthy C57BL/6 mice, induced relapsing paralysis with demyelinating immunopathologic features similar to multiple sclerosis. Second, the application of cholera toxin in the absence of autoantigen exacerbated the severity of conventional experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein in CFA. Third, the application of cholera toxin to the intact skin of NOD/Lt mice, with or without insulin B peptide 9-23, exacerbated insulitis and T lymphocyte-derived IFN-gamma and IL-4 production in the islets of Langerhans, resulting in an increased incidence and rate of onset of autoimmune diabetes. The data presented in this study highlight the different outcomes of adjuvant administration by different routes. Because dermal application of cholera toxin, and other bacterial products with similar adjuvant activities, is being developed as a clinical vaccination strategy, these data raise the possibility that it could precipitate autoimmune disease in genetically susceptible humans.
Riminton
D Sean
DS
Comparative Genomics Centre, James Cook University, Townsville, Queensland 4811, Australia.
Kandasamy
Rama
R
Dravec
Danijela
D
Basten
Antony
A
Baxter
Alan G
AG
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000279:Administration, Cutaneous; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D002772:Cholera Toxin / Q000008:administration & dosage* / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D007328:Insulin / Q000008:administration & dosage / Q000276:immunology; D007330:Insulin Antibodies / Q000096:biosynthesis; D007515:Islets of Langerhans / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009928:Organ Specificity / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D012720:Severity of Illness Index; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007328:Insulin; D007330:Insulin Antibodies; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D017778:Vaccines, Combined; C097877:insulin B (9-23); D002772:Cholera Toxin