HIV Skews a Balanced Mtb-Specific Th17 Response in Latent Tuberculosis Subjects to a Pro-inflammatory Profile Independent of Viral Load

Cell Rep. 2020 Dec 1;33(9):108451. doi: 10.1016/j.celrep.2020.108451.


HIV infection predisposes latent tuberculosis-infected (LTBI) subjects to active TB. This study is designed to determine whether HIV infection of LTBI subjects compromises the balanced Mycobacterium tuberculosis (Mtb)-specific T helper 17 (Th17) response of recognized importance in anti-TB immunity. Comparative analysis of Mtb- and cytomegalovirus (CMV)-specific CD4+ T cell responses demonstrates a marked dampening of the Mtb-specific CD4+ T cell effectors and polyfunctional cells while preserving CMV-specific response. Additionally, HIV skews the Mtb-specific Th17 response in chronic HIV-infected LTBI progressors, but not long-term non-progressors (LTNPs), with preservation of pro-inflammatory interferon (IFN)-γ+/interleukin-17+ (IL-17+) and significant loss of anti-inflammatory IL-10+/IL-17+ effectors that is restored by anti-retroviral therapy (ART). HIV-driven impairment of Mtb-specific response cannot be attributed to preferential infection as cell-associated HIV DNA and HIV RNA reveal equivalent viral burden in CD4+ T cells from different antigen specificities. We therefore propose that beyond HIV-induced loss of Mtb-specific CD4+ T cells, the associated dysregulation of Mtb-specific T cell homeostasis can potentially enhance the onset of TB in LTBI subjects.

Keywords: ART; ATT; CD4+ T cells; CD8+ T cells; HIV; HIV DNA/RNA; Long-term-non-progressors; Th17; pro-inflammatory; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • HIV Infections / genetics*
  • Humans
  • Interleukin-17 / metabolism*
  • Latent Tuberculosis / complications*
  • Male
  • Viral Load / methods*
  • Young Adult


  • IL17A protein, human
  • Interleukin-17