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HIV-tuberculosis-associated immune reconstitution inflammatory syndrome is characterized by Toll-like receptor and inflammasome signalling.
Lai, Rachel P J; Meintjes, Graeme; Wilkinson, Katalin A; Graham, Christine M; Marais, Suzaan; Van der Plas, Helen; Deffur, Armin; Schutz, Charlotte; Bloom, Chloe; Munagala, Indira; Anguiano, Esperanza; Goliath, Rene; Maartens, Gary; Banchereau, Jacques; Chaussabel, Damien; O'Garra, Anne; Wilkinson, Robert J.
Afiliación
  • Lai RPJ; The Francis Crick Institute Mill Hill Laboratory, London NW7 1AA, UK.
  • Meintjes G; Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Anzio Road, Observatory 7925, South Africa.
  • Wilkinson KA; Department of Medicine, Imperial College London, London W2 1PG, UK.
  • Graham CM; The Francis Crick Institute Mill Hill Laboratory, London NW7 1AA, UK.
  • Marais S; Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Anzio Road, Observatory 7925, South Africa.
  • Van der Plas H; The Francis Crick Institute Mill Hill Laboratory, London NW7 1AA, UK.
  • Deffur A; Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Anzio Road, Observatory 7925, South Africa.
  • Schutz C; Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Anzio Road, Observatory 7925, South Africa.
  • Bloom C; Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Anzio Road, Observatory 7925, South Africa.
  • Munagala I; Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Anzio Road, Observatory 7925, South Africa.
  • Anguiano E; The Francis Crick Institute Mill Hill Laboratory, London NW7 1AA, UK.
  • Goliath R; Baylor Institute for Immunology Research, Dallas, Texas 75204, USA.
  • Maartens G; Baylor Institute for Immunology Research, Dallas, Texas 75204, USA.
  • Banchereau J; Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Anzio Road, Observatory 7925, South Africa.
  • Chaussabel D; Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine and Department of Medicine, University of Cape Town, Anzio Road, Observatory 7925, South Africa.
  • O'Garra A; Baylor Institute for Immunology Research, Dallas, Texas 75204, USA.
  • Wilkinson RJ; Systems Immunology, Benaroya Research Institute, Seattle, Washington 98101, USA.
Nat Commun ; 6: 8451, 2015 Sep 24.
Article en En | MEDLINE | ID: mdl-26399326
Patients with HIV-associated tuberculosis (TB) initiating antiretroviral therapy (ART) may develop immune reconstitution inflammatory syndrome (TB-IRIS). No biomarkers for TB-IRIS have been identified and the underlying mechanisms are unclear. Here we perform transcriptomic profiling of the blood samples of patients with HIV-associated TB. We identify differentially abundant transcripts as early as week 0.5 post ART initiation that predict downstream activation of proinflammatory cytokines in patients who progress to TB-IRIS. At the characteristic time of TB-IRIS onset (week 2), the signature is characterized by over-representation of innate immune mediators including TLR signalling and TREM-1 activation of the inflammasome. In keeping with the transcriptional data, concentrations of plasma cytokines and caspase-1/5 are elevated in TB-IRIS. Inhibition of MyD88 adaptor and group 1 caspases reduces secretion of cytokines including IL-1 in TB-IRIS patients. These data provide insight on the pathogenesis of TB-IRIS and may assist the development of specific therapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / Infecciones por VIH / Citocinas / Receptores Toll-Like / Síndrome Inflamatorio de Reconstitución Inmune / Inflamasomas Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / Infecciones por VIH / Citocinas / Receptores Toll-Like / Síndrome Inflamatorio de Reconstitución Inmune / Inflamasomas Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2015 Tipo del documento: Article Pais de publicación: Reino Unido