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Short-term HIV-1 treatment interruption is associated with dysregulated TLR-stimuli responsiveness.

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Author

Summary, in English

Viremia during human immunodeficiency virus type-1 (HIV-1) infection results in progressive impairment of several components of the immune system. Here a unique model of repeated treatment interruptions (TIs) was used with the aim to reveal the effect of controlled short-term viremia on innate stimuli responsiveness and circulating dendritic cells (DCs). Sequential peripheral blood samples from HIV-1-infected patients on combination antiretroviral therapy, subjected to repeated TI cycles as part of a therapeutic DNA vaccination study, were analyzed. In vitro responsiveness of peripheral blood mononuclear cells to toll-like receptor (TLR) stimuli was analyzed by cytokine secretion, and frequencies of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were monitored by flow cytometry. These parameters were found not to be significantly different between the vaccinated and placebo groups. Instead, independent of vaccination altered in vitro TLR responsiveness was observed in parallel with TI cycles. TLR7/8-triggered secretion of IL-12 and IFN-α, as well as TLR9-triggered secretion of IL-12, was hyperactivated. In contrast, expression of IFN-α after TLR9 stimulation decreased during the initial cycle of TI. Reduced frequencies of pDCs and mDCs, compared with baseline, were noted before and during the second TI, respectively. Furthermore, spontaneous ex vivo release of IL-12 from PBMC was noted during cycles of TI. In conclusion, these results suggest that consequences of short-term TI include dysregulated TLR responses and fluctuations in the frequencies of circulating DCs. Knowledge of these immunological factors may influence the continuation of stringent treatment schedules during HIV infections.

Publishing year

2013

Language

English

Pages

2103-2110

Publication/Series

Human Vaccines & Immunotherapeutics

Volume

9

Issue

10

Document type

Journal article

Publisher

Taylor & Francis

Topic

  • Microbiology in the medical area
  • Pharmacology and Toxicology

Keywords

  • DNA: immunology
  • DNA: administration & dosage
  • Vaccines
  • Toll-Like Receptors: immunology
  • HIV-1: immunology
  • HIV Infections: immunology
  • HIV Infections: drug therapy
  • Dendritic Cells: immunology
  • Anti-HIV Agents: therapeutic use
  • AIDS Vaccines: administration & dosage
  • AIDS Vaccines: immunology
  • Viremia: immunology
  • Viremia: virology

Status

Published

ISBN/ISSN/Other

  • ISSN: 2164-5515