Wilkinson, KA;
Schneider-Luftman, D;
Lai, R;
Barrington, C;
Jhilmeet, N;
Lowe, DM;
Kelly, G;
(2021)
Antiretroviral Treatment-Induced Decrease in Immune Activation Contributes to Reduced Susceptibility to Tuberculosis in HIV-1/Mtb Co-infected Persons.
Frontiers in Immunology
, 12
, Article 645446. 10.3389/fimmu.2021.645446.
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Antiretroviral Treatment-Induced Decrease in Immune Activation Contributes to Reduced Susceptibility to Tuberculosis in HIV-.pdf - Published Version Download (985kB) | Preview |
Abstract
Antiretroviral treatment (ART) reduces the risk of developing active tuberculosis (TB) in HIV-1 co-infected persons. In order to understand host immune responses during ART in the context of Mycobacterium tuberculosis (Mtb) sensitization, we performed RNAseq analysis of whole blood-derived RNA from individuals with latent TB infection coinfected with HIV-1, during the first 6 months of ART. A significant fall in RNA sequence abundance of the Hallmark IFN-alpha, IFN-gamma, IL-6/JAK/STAT3 signaling, and inflammatory response pathway genes indicated reduced immune activation and inflammation at 6 months of ART compared to day 0. Further exploratory evaluation of 65 soluble analytes in plasma confirmed the significant decrease of inflammatory markers after 6 months of ART. Next, we evaluated 30 soluble analytes in QuantiFERON Gold in-tube (QFT) samples from the Ag stimulated and Nil tubes, during the first 6 months of ART in 30 patients. There was a significant decrease in IL-1alpha and IL-1beta (Ag-Nil) concentrations as well as MCP-1 (Nil), supporting decreased immune activation and inflammation. At the same time, IP-10 (Ag-nil) concentrations significantly increased, together with chemokine receptor-expressing CD4 T cell numbers. Our data indicate that ART-induced decrease in immune activation combined with improved antigen responsiveness may contribute to reduced susceptibility to tuberculosis in HIV-1/Mtb co-infected persons.
| Type: | Article |
|---|---|
| Title: | Antiretroviral Treatment-Induced Decrease in Immune Activation Contributes to Reduced Susceptibility to Tuberculosis in HIV-1/Mtb Co-infected Persons |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2021.645446 |
| Publisher version: | http://dx.doi.org/10.3389/fimmu.2021.645446 |
| Language: | English |
| Additional information: | Copyright © 2021 Wilkinson, Schneider-Luftman, Lai, Barrington, Jhilmeet, Lowe, Kelly and Wilkinson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | Immunology, antiretroviral treatment, tuberculosis, plasma biomarker, RNAseq, QuantiFERON |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10132347 |
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