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Interferon regulatory factor 1 is essential for pathogenic CD8+ T cell migration and retention in the brain during experimental cerebral malaria.
Gun, Sin Yee; Claser, Carla; Teo, Teck Hui; Howland, Shanshan W; Poh, Chek Meng; Chye, Rebecca Ren Ying; Ng, Lisa F P; Rénia, Laurent.
Afiliação
  • Gun SY; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore.
  • Claser C; Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Teo TH; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore.
  • Howland SW; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore.
  • Poh CM; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore.
  • Chye RRY; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore.
  • Ng LFP; Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
  • Rénia L; Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore.
Cell Microbiol ; 20(5): e12819, 2018 05.
Article em En | MEDLINE | ID: mdl-29281764
ABSTRACT
Host immune response has a key role in controlling the progression of malaria infection. In the well-established murine model of experimental cerebral malaria (ECM) with Plasmodium berghei ANKA infection, proinflammatory Th1 and CD8+ T cell response are essential for disease development. Interferon regulatory factor 1 (IRF1) is a transcription factor that promotes Th1 responses, and its absence was previously shown to protect from ECM death. Yet the exact mechanism of protection remains unknown. Here we demonstrated that IRF1-deficient mice (IRF1 knockout) were protected from ECM death despite displaying early neurological signs. Resistance to ECM death was a result of reduced parasite sequestration and pathogenic CD8+ T cells in the brain. Further analysis revealed that IRF1 deficiency suppress interferon-γ production and delayed CD8+ T cell proliferation. CXCR3 expression was found to be decreased in pathogenic CD8+ T cells, which limited their migration to the brain. In addition, reduced expression of adhesion molecules by brain endothelial cells hampered leucocyte retention in the brain. Taken together, these factors limited sequestration of pathogenic CD8+ T cells and consequently its ability to induce extensive damage to the blood-brain barrier.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Plasmodium berghei / Malária Cerebral / Fator Regulador 1 de Interferon / Receptores CXCR3 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Microbiol Assunto da revista: MICROBIOLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Singapura

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Plasmodium berghei / Malária Cerebral / Fator Regulador 1 de Interferon / Receptores CXCR3 Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cell Microbiol Assunto da revista: MICROBIOLOGIA Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Singapura