IL-27R signalling mediates early viral containment and impacts innate and adaptive immunity after chronic lymphocytic choriomeningitis virus infection
Autor: | Harker, J, Wong, K, Dallari, S, Bao, P, Dolgoter, A, Jo, Y, Wehrens, E, Macal, M, Zuniga, E |
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Přispěvatelé: | Wellcome Trust |
Rok vydání: | 2018 |
Předmět: |
CD4(+) T-CELLS
Interleukin-27 HIV-1 INFECTION T cells Adaptive Immunity Lymphocytic Choriomeningitis HUMAN MACROPHAGES DCs IL-27 NATURAL-KILLER-CELLS Mice Virology Animals Lymphocytic choriomeningitis virus dendritic cells Receptors Cytokine LCMV Mice Knockout Science & Technology CUTTING EDGE I INTERFERON NKT CELLS hemic and immune systems 11 Medical And Health Sciences 06 Biological Sciences chronic infection cytokines PERSISTENT LCMV INFECTION Immunity Innate Killer Cells Natural Mice Inbred C57BL HELPER-CELLS PLASMACYTOID DENDRITIC CELLS Chronic Disease 07 Agricultural And Veterinary Sciences Life Sciences & Biomedicine antibody function type I IFN Signal Transduction |
Popis: | Chronic viral infections represent a major challenge to host's immune response and a unique network of immunological elements, including cytokines, are required for their containment. By using a model persistent infection with the natural murine pathogen lymphocytic choriomeningitis virus clone 13 (LCMV Cl13) we investigated the role of one such cytokine, interleukin 27 (IL-27), in the control of chronic infection. We found that IL-27R signalling promoted control of LCMV Cl13 as early as day 1 and 5 after infection and that il27p28 transcripts were rapidly elevated in multiple subsets of dendritic cells (DCs) and myeloid cells. In particular, plasmacytoid DCs (pDCs), the most potent type-1-interferon (IFN-I) producing cells, significantly increased il27p28 in a TLR7 dependent fashion. Notably, mice deficient in IL-27 specific receptor (R), WSX-1, exhibited a pleiotropy of innate and adaptive immune alterations after chronic LCMV infection, including compromised NK cell cytotoxicity and antibody responses. While, the majority of these immune alterations appeared cell-extrinsic, cell-intrinsic IL-27R was necessary to maintain early pDC numbers, which, alongside lower IFN-I transcription in CD11b+ DCs and myeloid cells, may explain the compromised IFN-I elevation that we observed early after LCMV Cl13 infection in IL-27R-deficient mice. Together these data highlight the critical role of IL-27 in enabling optimal anti-viral immunity early and late after infection with a systemic persistent virus and suggest that a previously unrecognized positive feedback-loop mediated by IL-27 in pDCs might be involved in this process. |
Databáze: | OpenAIRE |
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