Dysregulation of the immune environment in the airways during HIV infection
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Published version
Author(s)
Type
Journal Article
Abstract
HIV-1 increases susceptibility to pulmonary infection and disease, suggesting pathogenesis in the lung. However, the lung immune environment during HIV infection remains poorly characterized. This study examined T cell activation and the cytokine milieu in paired bronchoalveolar lavage (BAL) and blood from 36 HIV-uninfected and 32 HIV-infected participants. Concentrations of 27 cytokines were measured by Luminex, and T cells were phenotyped by flow cytometry. Blood and BAL had distinct cytokine profiles (p=0.001). In plasma, concentrations of inflammatory cytokines like IFN-γ (p=0.004) and TNF-α (p=0.004) were elevated during HIV infection, as expected. Conversely, BAL cytokine concentrations were similar in HIV-infected and uninfected individuals, despite high BAL viral loads (VL; median 48,000 copies/ml epithelial lining fluid). HIV-infected individuals had greater numbers of T cells in BAL compared to uninfected individuals (p=0.007); and BAL VL positively associated with CD4+ and CD8+ T cell numbers (p=0.006 and p=0.0002, respectively) and CXCL10 concentrations (p=0.02). BAL T cells were highly activated in HIV-infected individuals, with nearly 2-3 fold greater frequencies of CD4+CD38+ (1.8-fold; p=0.007), CD4+CD38+HLA-DR+ (1.9-fold; p=0.0006), CD8+CD38+ (2.8-fold; p=0.0006), CD8+HLA-DR+ (2-fold; p=0.022) and CD8+CD38+HLA-DR+ (3.6-fold; p<0.0001) cells compared to HIV-uninfected individuals. Overall, this study demonstrates a clear disruption of the pulmonary immune environment during HIV infection, with readily detectable virus and activated T lymphocytes, which may be driven to accumulate by local chemokines.
Date Issued
2021-06-30
Date Acceptance
2021-06-17
Citation
Frontiers in Immunology, 2021, 12, pp.1-12
ISSN
1664-3224
Publisher
Frontiers Media
Start Page
1
End Page
12
Journal / Book Title
Frontiers in Immunology
Volume
12
Copyright Statement
© 2021 Bunjun, Soares, Thawer, Müller, Kiravu, Ginbot, Corleis, Murugan, Kwon, von Groote-Bidlingmaier, Riou, Wilkinson, Walzl and Burgers. 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.
License URL
Sponsor
Wellcome Trust
Wellcome Trust
Identifier
https://www.frontiersin.org/articles/10.3389/fimmu.2021.707355/full
Grant Number
104803/Z/14/Z
WDAI_P83556
Subjects
1107 Immunology
1108 Medical Microbiology
Publication Status
Published
Article Number
707355
Date Publish Online
2021-06-30