Viral delivery of an epitope from Haemophilus influenzae induces central nervous system autoimmune disease by molecular mimicry

J. Ludovic Croxford, Holly A. Anger, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Multiple sclerosis (MS) is an autoimmune CNS demyelinating disease in which infection may be an important initiating factor. Pathogen-induced cross-activation of autoimmune T cells may occur by molecular mimicry. Infection with wild-type Theiler's murine encephalomyelitis virus induces a late-onset, progressive T cell-mediated demyelinating disease, similar to MS. To determine the potential of virus-induced autoimmunity by molecular mimicry, a nonpathogenic neurotropic Theiler's murine encephalomyelitis virus variant was engineered to encode a mimic peptide from protease IV of Haemophilus influenzae (III), sharing 6 of 13 aa with the dominant encephalitogenic proteolipid protein (PLP) epitope PLP139-151. Infection of SJL mice with the HI mimic-expressing virus induced a rapid-onset, nonprogressive paralytic disease characterized by potent activation of self-reactive PLP139-151- specific CD4+ Th1 responses. In contrast, mice immunized with the HI mimic-peptide in CFA did not develop disease, associated with the failure to induce activation of PLP139-151-specific CD4+ Th1 cells. However, preinfection with the mimic-expressing virus before mimic-peptide immunization led to severe disease. Therefore, infection with a mimic-expressing virus directly initiates organ-specific T cell-mediated autoimmunity, suggesting that pathogen-delivered innate immune signals may play a crucial role in triggering differentiation of pathogenic self-reactive responses. These results have important implications for explaining the pathogenesis of MS and other autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)907-917
Number of pages11
JournalJournal of Immunology
Volume174
Issue number2
DOIs
StatePublished - Jan 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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