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Plasmacytoid dendritic cells control T-cell response to chronic viral infection

Cervantes-Barragan, Luisa
Lewis, Kanako L
Firner, Sonja
Thiel, Volker
Ludewig, Burkhard
Reizis, Boris
Published in Proceedings of the National Academy of Sciences. 2012, vol. 109, no. 8, p. 3012-7
Abstract Infections with persistent viruses are a frequent cause of immunosuppression, autoimmune sequelae, and/or neoplastic disease. Plasmacytoid dendritic cells (pDCs) are innate immune cells that produce type I interferon (IFN-I) and other cytokines in response to virus-derived nucleic acids. Persistent viruses often cause depletion or functional impairment of pDCs, but the role of pDCs in the control of these viruses remains unclear. We used conditional targeting of pDC-specific transcription factor E2-2 to generate mice that constitutively lack pDCs in peripheral lymphoid organs and tissues. The profound impact of pDC deficiency on innate antiviral responses was revealed by the failure to control acute infection with the cytopathic mouse hepatitis virus. Furthermore, pDC-deficient animals failed to clear lymphocytic choriomeningitis virus (LCMV) from hematopoietic organs during persistent LCMV infection. This failure was associated with reduced numbers and functionality of LCMV-specific CD4(+) helper T cells and impaired antiviral CD8(+) T-cell responses. Adoptive transfer of LCMV-specific T cells revealed that both CD4(+) and CD8(+) T cells required IFN-I for expansion, but only CD4(+) T cells required the presence of pDCs. In contrast, mice with pDC-specific loss of MHC class II expression supported normal CD4(+) T-cell response to LCMV. These data suggest that pDCs facilitate CD4(+) helper T-cell responses to persistent viruses independently of direct antigen presentation. Thus pDCs provide an essential link between innate and adaptive immunity to chronic viral infection, likely through the secretion of IFN-I and other cytokines.
Keywords AnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolismChronic DiseaseCoronavirus Infections/immunology/virologyDendritic Cells/immunologyDisease Models, AnimalGene TargetingLymphocytic Choriomeningitis/blood/immunology/prevention & control/virologyLymphocytic choriomeningitis virus/immunologyMiceMice, Inbred C57BLMurine hepatitis virus/immunologyT-Lymphocytes/immunologyVirus Diseases/immunology/virology
PMID: 22315415
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Research groups Groupe Reith Walter (pathologie et immunologie) (282)
Pathologie et immunologie (906)
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CERVANTES-BARRAGAN, Luisa et al. Plasmacytoid dendritic cells control T-cell response to chronic viral infection. In: Proceedings of the National Academy of Sciences, 2012, vol. 109, n° 8, p. 3012-7. doi: 10.1073/pnas.1117359109 https://archive-ouverte.unige.ch/unige:29175

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Deposited on : 2013-08-12

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