TLR signals license CD8 T cells to destroy oligodendrocytes expressing an antigen shared with a Listeria pathogen
| Autor: | Noelle K. Polakos, Martina Deckert, Tobias Blau, Manuel Montesinos-Rongen, Monica Sanchez-Ruiz, Anna Brunn, Thomas Hünig, Olaf Utermöhlen |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Central Nervous System Ovalbumin Immunology Biology CD8-Positive T-Lymphocytes Autoimmune Diseases 03 medical and health sciences 0302 clinical medicine Immune system Antigen Immunology and Allergy Cytotoxic T cell Animals Listeriosis Antigens Cells Cultured Toll-like receptor Innate immune system Toll-Like Receptors Listeria monocytogenes Mice Inbred C57BL TLR2 Oligodendroglia 030104 developmental biology TLR3 Myeloid Differentiation Factor 88 CD8 030215 immunology Demyelinating Diseases Signal Transduction |
| Zdroj: | European journal of immunology. 49(3) |
| ISSN: | 1521-4141 |
| Popis: | Increasing evidence suggests a role of CD8 T cells in autoimmune demyelinating CNS disease, which, however, is still controversially discussed. Mice, which express ovalbumin (OVA) as cytosolic self-antigen in oligodendrocytes (ODC-OVA mice), respond to CNS infection induced by OVA-expressing attenuated Listeria with CD8 T cell-mediated inflammatory demyelination. This model is suitable to decipher the contribution of CD8 T cells and the pathogen in autoimmune CNS disease. Here, we show that both antigen and pathogen are required in the CNS for disease induction, though not in a physically linked fashion. Intracerebral challenge with combined toll like receptor (TLR) TLR2 and TLR9 as well as TLR7 and TLR9 agonists substituted for the bacterial stimulus, but not with individual TLR agonists (TLR2, TLR3,TLR5,TLR7, TLR9). Furthermore, MyD88 inactivation rendered ODC-OVA mice resistant to disease induction. Collectively, CD8 T cell-mediated destruction of oligodendrocytes is activated if (i) an antigen shared with an infectious agent is provided in the CNS microenvironment and (ii) innate immune signals inform the CNS microenvironment that pathogen removal warrants an immune attack by CD8 T cells, even at the expense of locally restricted demyelination. |
| Databáze: | OpenAIRE |
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