@article{Wilkinson2021,
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.},
author = {Wilkinson, Katalin A and Schneider-Luftman, Deborah and Lai, Rachel and Barrington, Christopher and Jhilmeet, Nishtha and Lowe, David M. and Kelly, Gavin and Wilkinson, Robert J},
doi = {10.3389/fimmu.2021.645446},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wilkinson et al. - 2021 - Antiretroviral treatment-induced decrease in immune activation contributes to reduced susceptibility to tuberc.pdf:pdf},
issn = {1664-3224},
journal = {Frontiers in Immunology},
keywords = {OA,QuantiFERON,RNAseq,antiretroviral treatment,fund{\_}ack,original,plasma biomarker,tuberculosis},
mendeley-tags = {OA,fund{\_}ack,original},
month = {mar},
pages = {645446},
pmid = {33746987},
publisher = {Frontiers},
title = {{Antiretroviral treatment-induced decrease in immune activation contributes to reduced susceptibility to tuberculosis in HIV-1/Mtb co-infected persons}},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2021.645446/full},
volume = {12},
year = {2021}
}

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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. 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At the same time, IP-10 (Ag-nil) concentrations significantly increased, together with chemokine receptor-expressing CD4 T cell numbers. 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