Journal of NeuroVirology

, Volume 18, Issue 6, pp 471–478 | Cite as

Possible role of interleukin-17 in a prime/challenge model of multiple sclerosis

  • Jane E. Libbey
  • Ikuo Tsunoda
  • Robert S. Fujinami
Article
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Abstract

No one single pathogen has been identified as the causative agent of multiple sclerosis (MS). Alternately, the likelihood of an autoimmune event may be nonspecifically enhanced by different infectious agents. In a novel animal model of MS, SJL/J mice primed through infection with a recombinant vaccinia virus (VV) encoding myelin proteolipid protein (PLP) (VVPLP) were susceptible to a central nervous system (CNS) inflammatory disease following administration of a nonspecific immunostimulant [complete Freund’s adjuvant (CFA) plus Bordetella pertussis (BP)]. Mononuclear cells isolated from the brains, but not the spleens, of VVPLP-primed CFA/BP challenged mice produced interleukin (IL)-17 and interferon-γ and transferred a CNS inflammatory disease to naïve SJL/J mice. Administration of curdlan, a T helper 17 cell inducer, unexpectedly resulted in less severe clinical and histological signs of disease, compared to CFA/BP challenged mice, despite the induction of IL-17 in the periphery. Further examination of the VVPLP-prime CFA/BP challenge model may suggest new mechanisms for how different pathogens associated with MS can protect or enhance disease.

Keywords

Autoimmunity CNS inflammatory demyelinating diseases Experimental autoimmune encephalomyelitis Multiple sclerosis Theiler’s murine encephalomyelitis virus Vaccination 
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Notes

Acknowledgments

We thank J. Lindsay Whitton, MD, PhD, and Matthew F. Cusick, PhD, for many helpful discussions, and Nikki J. Kennett, MS, Daniel J. Doty, BS, Braden T. McElreath, Lincoln R. Neugebauer and Robert Greenhalgh, BS, for excellent technical assistance. We are grateful to Mr. Daniel J. Harper for preparation of the manuscript. This work was supported by NIH grants AI058105-05 (RSF), R21NS059724, P20-RR018724 and 8P20 GM103433-10 (IT).

References

  1. Barnett LA, Whitton JL, Wada Y, Fujinami RS (1993) Enhancement of autoimmune disease using recombinant vaccinia virus encoding myelin proteolipid protein [published erratum appears in J Neuroimmunol 48:120, 1993]. J Neuroimmunol 44:15–25PubMedCrossRefGoogle Scholar
  2. Chen SJ, Wang YL, Fan HC, Lo WT, Wang CC, Sytwu HK (2012) Current status of the immunomodulation and immunomediated therapeutic strategies for multiple sclerosis. Clin Dev Immunol 2012:970789. doi: 10.1155/2012/970789 PubMedGoogle Scholar
  3. Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517. doi: 10.1016/S0140-6736(08)61620-7 PubMedCrossRefGoogle Scholar
  4. Cusick MF, Libbey JE, Fujinami RS (2012) Molecular mimicry as a mechanism of autoimmune disease. Clin Rev Allergy Immunol 42:102–111. doi: 10.1007/s12016-011-8294-7 PubMedCrossRefGoogle Scholar
  5. Fletcher JM, Lalor SJ, Sweeney CM, Tubridy N, Mills KHG (2010) T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol 162:1–11. doi: 10.1111/j.1365-2249.2010.04143.x PubMedCrossRefGoogle Scholar
  6. Fujinami RS (2001) Viruses and autoimmune disease—two sides of the same coin? Trends Microbiol 9:377–381. doi: 10.1016/S0966-842X(01)02097-2 PubMedCrossRefGoogle Scholar
  7. Fujinami RS, Oldstone MBA (1985) Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science 230:1043–1045PubMedCrossRefGoogle Scholar
  8. Fujinami RS, Oldstone MBA, Wroblewska Z, Frankel ME, Koprowski H (1983) Molecular mimicry in virus infection: crossreaction of measles virus phosphoprotein or of herpes simplex virus protein with human intermediate filaments. Proc Natl Acad Sci USA 80:2346–2350PubMedCrossRefGoogle Scholar
  9. Gran B, Zhang G-X, Rostami A (2004) Role of the IL-12/IL-23 system in the regulation of T-cell responses in central nervous system inflammatory demyelination. Crit Rev Immunol 24:111–128PubMedCrossRefGoogle Scholar
  10. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132. doi: 10.1038/ni1254 PubMedCrossRefGoogle Scholar
  11. Hou W, Kang HS, Kim BS (2009) Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection. J Exp Med 206:313–328. doi: 10.1084/jem.20082030 PubMedCrossRefGoogle Scholar
  12. Jadidi-Niaragh F, Mirshafiey A (2011) Th17 cell, the new player of neuroinflammatory process in multiple sclerosis. Scand J Immunol 74:1–13. doi: 10.1111/j.1365-3083.2011.02536.x PubMedCrossRefGoogle Scholar
  13. Kriesel JD, Sibley WA (2005) Editorial: the case for rhinoviruses in the pathogenesis of multiple sclerosis. Mult Scler 11:1–4PubMedCrossRefGoogle Scholar
  14. Laroche C, Michaud P (2007) New developments and prospective applications for β (1,3) glucans. Recent Pat Biotechnol 1:59–73PubMedCrossRefGoogle Scholar
  15. LeibundGut-Landmann S, Gross O, Robinson MJ, Osorio F, Slack EC, Tsoni SV, Schweighoffer E, Tybulewicz V, Brown GD, Ruland J, Reis e Sousa C (2007) Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol 8:630–638. doi: 10.1038/ni1460 PubMedCrossRefGoogle Scholar
  16. Libbey JE, Fujinami RS (2010) Potential triggers of MS. Results Probl Cell Differ 51:21–42. doi: 10.1007/400_2008_12 PubMedCrossRefGoogle Scholar
  17. Libbey JE, McCoy LL, Fujinami RS (2007) Molecular mimicry in multiple sclerosis. Int Rev Neurobiol 79:127–147. doi: 10.1016/S0074-7742(07)79006-2 PubMedCrossRefGoogle Scholar
  18. Libbey JE, Tsunoda I, Fujinami RS (2010) Studies in the modulation of experimental autoimmune encephalomyelitis. J Neuroimmune Pharmacol 5:168–175. doi: 10.1007/s11481-010-9215-x PubMedCrossRefGoogle Scholar
  19. McCoy L, Tsunoda I, Fujinami RS (2006) Multiple sclerosis and virus induced immune responses: autoimmunity can be primed by molecular mimicry and augmented by bystander activation. Autoimmunity 39:9–19. doi: 10.1080/08916930500484799 PubMedCrossRefGoogle Scholar
  20. McIntosh M, Stone BA, Stanisich VA (2005) Curdlan and other bacterial (1→3)-β-d-glucans. Appl Microbiol Biotechnol 68:163–173. doi: 10.1007/s00253-005-1959-5 PubMedCrossRefGoogle Scholar
  21. Petermann F, Korn T (2011) Cytokines and effector T cell subsets causing autoimmune CNS disease. FEBS Lett 585:3747–3757. doi: 10.1016/j.febslet.2011.03.064 PubMedCrossRefGoogle Scholar
  22. Pullen LC, Miller SD, Dal Canto MC, Van der Meide PH, Kim BS (1994) Alteration in the level of interferon-gamma results in acceleration of Theiler’s virus-induced demyelinating disease. J Neuroimmunol 55:143–152PubMedCrossRefGoogle Scholar
  23. Rauch HC, Montgomery IN, Hinman CL, Harb W, Benjamins JA (1987) Chronic Theiler’s virus infection in mice: appearance of myelin basic protein in the cerebrospinal fluid and serum antibody directed against MBP. J Neuroimmunol 14:35–48. doi: 10.1016/0165-5728(87)90099-3 PubMedCrossRefGoogle Scholar
  24. Theil DJ, Tsunoda I, Rodriguez F, Whitton JL, Fujinami RS (2001) Viruses can silently prime for and trigger central nervous system autoimmune disease. J NeuroVirol 7:220–227. doi: 10.1080/13550280152403263 PubMedCrossRefGoogle Scholar
  25. Tsunoda I, Fujinami RS (1996) Two models for multiple sclerosis: experimental allergic encephalomyelitis and Theiler’s murine encephalomyelitis virus. J Neuropathol Exp Neurol 55:673–686PubMedCrossRefGoogle Scholar
  26. Tsunoda I, Fujinami RS (1999) Theiler’s murine encephalomyelitis virus. In: Ahmed R, Chen ISY (eds) Persistent viral infections. Wiley, Chichester, pp 517–536Google Scholar
  27. Tsunoda I, Kuang L-Q, Tolley ND, Whitton JL, Fujinami RS (1998) Enhancement of experimental allergic encephalomyelitis (EAE) by DNA immunization with myelin proteolipid protein (PLP) plasmid DNA. J Neuropathol Exp Neurol 57:758–767PubMedCrossRefGoogle Scholar
  28. Tsunoda I, Kuang L-Q, Theil DJ, Fujinami RS (2000) Antibody association with a novel model for primary progressive multiple sclerosis: induction of relapsing-remitting and progressive forms of EAE in H2 S mouse strains. Brain Pathol 10:402–418PubMedCrossRefGoogle Scholar
  29. Tsunoda I, Wada Y, Libbey JE, Cannon TS, Whitby FG, Fujinami RS (2001) Prolonged gray matter disease without demyelination caused by Theiler’s murine encephalomyelitis virus with a mutation in VP2 puff B. J Virol 75:7494–7505. doi: 10.1128/JVI.75.16.7494-7505.2001 PubMedCrossRefGoogle Scholar
  30. Tsunoda I, Libbey JE, Fujinami RS (2007) Sequential polymicrobial infections lead to CNS inflammatory disease: possible involvement of bystander activation in heterologous immunity. J Neuroimmunol 188:22–33. doi: 10.1016/j.jneuroim.2007.05.012 PubMedCrossRefGoogle Scholar
  31. von Herrath MG, Fujinami RS, Whitton JL (2003) Microorganisms and autoimmunity: making the barren field fertile? Nat Rev Microbiol 1:151–157. doi: 10.1038/nrmicro754 CrossRefGoogle Scholar
  32. Yoshitomi H, Sakaguchi N, Kobayashi K, Brown GD, Tagami T, Sakihama T, Hirota K, Tanaka S, Nomura T, Miki I, Gordon S, Akira S, Nakamura T, Sakaguchi S (2005) A role for fungal β-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice. J Exp Med 201:949–960. doi: 10.1084/jem.20041758 PubMedCrossRefGoogle Scholar
  33. Zepp J, Wu L, Li X (2011) IL-17 receptor signaling and T helper 17-mediated autoimmune demyelinating disease. Trends Immunol 32:232–239. doi: 10.1016/j.it.2011.02.007 PubMedCrossRefGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2012

Authors and Affiliations

  • Jane E. Libbey
    • 1
  • Ikuo Tsunoda
    • 2
    • 3
  • Robert S. Fujinami
    • 1
  1. 1.Department of PathologyUniversity of Utah School of MedicineSalt Lake CityUSA
  2. 2.Department of Microbiology and ImmunologyLouisiana State University Health Sciences CenterShreveportUSA
  3. 3.Center for Molecular & Tumor VirologyLouisiana State University Health Sciences CenterShreveportUSA

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