Human immunodeficiency virus infection impairs Th1 and Th17 mycobacterium tuberculosis–specific T-Cell responses

Lyle W. Murray, Iman Satti, Jodi Meyerowitz, Matthew Jones, Christian B. Willberg, James E. Ussher, Dominique Goedhals, Jacob Hurst, Rodney E. Phillips, Helen McShane, Cloete van Vuuren, John Frater

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Background. Human immunodeficiency virus (HIV)–infected individuals have a higher risk of developing active tuberculosis (TB) than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (Mtb)–specific CD4+ and CD8+ T-cell responses contributed to this increased risk. Methods. Mtb-specific T-cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa, were evaluated. Using a whole-blood flow cytometry assay, we measured expression of interferon gamma, tumor necrosis factor alpha, interleukin 2, and interleukin 17 in CD4+ and CD8+ T cells in response to Mtb antigens (PPD, ESAT-6/CFP-10 [EC], and DosR regulon-encoded α-crystallin [Rv2031c]). Results. Fewer HIV-infected individuals had detectable CD4+ and CD8+ T-cell responses to PPD and Rv2031c than HIV-uninfected subjects. Mtb-specific T cells showed distinct patterns of cytokine expression comprising both Th1 (CD4 and CD8) and Th17 (CD4) cytokines, the latter at highest frequency for Rv2031c. Th17 antigen-specific responses to all antigens tested were specifically impaired in HIV-infected individuals. Conclusions. HIV-associated impairment of CD4+ and CD8+ Mtb-specific T-cell responses is antigen specific, particularly impacting responses to PPD and Rv2031c. Preferential depletion of Th17 cytokine-expressing CD4+ T cells suggests this T-cell subset may be key to TB susceptibility in HIV-infected individuals.

Original languageEnglish
Pages (from-to)1782-1792
Number of pages11
JournalJournal of Infectious Diseases
Volume217
Issue number11
DOIs
Publication statusPublished - 1 Jun 2018
Externally publishedYes

Bibliographical note

Funding Information:
Financial support. This work was supported by a Medical Research Council Senior Fellowship (to J. F.) and a Rhodes Scholarship award (to L. M.). Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.

Keywords

  • HIV
  • Immune responses
  • Mycobacterium tuberculosis
  • Th1
  • Th17

Fingerprint

Dive into the research topics of 'Human immunodeficiency virus infection impairs Th1 and Th17 mycobacterium tuberculosis–specific T-Cell responses'. Together they form a unique fingerprint.

Cite this