56
IRUS Total
Downloads

HIV-tuberculosis-associated immune reconstitution inflammatory syndrome is characterized by Toll-like receptor and inflammasome signalling

Title: HIV-tuberculosis-associated immune reconstitution inflammatory syndrome is characterized by Toll-like receptor and inflammasome signalling
Authors: Lai, RPJ
Meintjes, G
Wilkinson, KA
Graham, CM
Marais, S
Van der Plas, H
Deffur, A
Schutz, C
Bloom, C
Munagala, I
Anguiano, E
Goliath, R
Maartens, G
Banchereau, J
Chaussabel, D
O'Garra, A
Wilkinson, RJ
Item Type: Journal Article
Abstract: 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.
Issue Date: 24-Sep-2015
Date of Acceptance: 21-Aug-2015
URI: http://hdl.handle.net/10044/1/33888
DOI: 10.1038/ncomms9451
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 6
Issue: 10
Copyright Statement: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Sponsor/Funder: Wellcome Trust
Funder's Grant Number: 104803/Z/14/Z
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MYCOBACTERIUM-TUBERCULOSIS
INFECTED PATIENTS
ANTIRETROVIRAL THERAPY
NLRP3 INFLAMMASOME
INTERFERON-GAMMA
ACTIVATION
MACROPHAGES
INNATE
INTERLEUKIN-1
RESPONSES
Adult
Antiretroviral Therapy, Highly Active
Caspase 1
Caspases
Cytokines
Female
Gene Expression Profiling
HIV Infections
Humans
Immune Reconstitution Inflammatory Syndrome
Immunity, Innate
Inflammasomes
Inflammation Mediators
Interleukin-1
Leukocytes, Mononuclear
Male
Membrane Glycoproteins
Receptors, Immunologic
Receptors, Interleukin-1
Toll-Like Receptors
Triggering Receptor Expressed on Myeloid Cells-1
Tuberculosis
Young Adult
Leukocytes, Mononuclear
Humans
Tuberculosis
HIV Infections
Caspases
Caspase 1
Membrane Glycoproteins
Receptors, Immunologic
Receptors, Interleukin-1
Inflammation Mediators
Interleukin-1
Cytokines
Antiretroviral Therapy, Highly Active
Gene Expression Profiling
Adult
Female
Male
Toll-Like Receptors
Immune Reconstitution Inflammatory Syndrome
Immunity, Innate
Young Adult
Inflammasomes
Triggering Receptor Expressed on Myeloid Cells-1
Publication Status: Published
Article Number: ARTN 8451
Appears in Collections:Department of Infectious Diseases
National Heart and Lung Institute
Faculty of Medicine