Nanotechnology as a New Therapeutic Approach to Prevent the HIV-Infection of Treg Cells

PLoS One. 2016 Jan 19;11(1):e0145760. doi: 10.1371/journal.pone.0145760. eCollection 2016.

Abstract

Background: HIV-1 has proved to infect regulatory T cells (Treg) modifying their phenotype and impairing their suppressive capacity. As Treg cells are a crucial component in the preservation of the immune homeostasis, we researched that the antiviral capacity of carboxilan dendrimers prevents the HIV-1 infection of Treg and their effects. The phenotype and suppressive capacity of Treg treated or non-treated with carbosilane dendrimers were studied by flow cytometry. Treated and non-treated Treg from healthy donors were infected with HIV-1NL4.3. The infection of Treg cells by HIV-1, and protective effect of two dendrimers were determined by measuring antigen p24gag in the supernatant of the culture and intracellular.

Results: The Treg cells were treated with cationic and anionic carbosilane dendrimers. The results showed that both dendrimers did not modify the phenotype and functionality of Treg cells compared with non- treated Treg cells. Anionic dendrimers showed high biocompatibility with normal activity of the Treg cells and in antiviral assays. These dendrimers were highly active against HIV-1 preventing the infection of Treg, and were able to protect the Treg from the Foxp3 downregulation induced by the HIV-1 infection.

Conclusions: This is the first work showing that the in vitro use of anionic dendrimers prevent the HIV-1 replication and the infection of expanded Treg cells in culture, which raises the possibility to use Treg cells therapeutically in HIV-1-infected subjects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Surface / metabolism
  • Cell Survival
  • Cells, Cultured
  • Dendrimers / chemistry
  • Dendrimers / pharmacology
  • Forkhead Transcription Factors / metabolism
  • HIV Infections / immunology*
  • HIV Infections / therapy
  • HIV Infections / virology*
  • HIV-1 / physiology
  • Humans
  • Immunomodulation / drug effects
  • Immunophenotyping
  • Nanomedicine* / methods
  • Nanotechnology*
  • Phenotype
  • Silanes / chemistry
  • Silanes / pharmacology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / virology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / virology*

Substances

  • Antigens, Surface
  • Dendrimers
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Silanes
  • carbosilane

Grants and funding

This work has been (partially) funded by the RD12/0017/0037, project as part of the Plan Nacional R+D+I and cofinanced by ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), RETIC PT13/0010/0028, Fondo de Investigacion Sanitaria (FIS) (grant numbers PI12-00934, PI13/02016), CTQ2011-23245 (MIMECO), “Fundación para la Investigación y la Prevención del Sida en España” (FIPSE), Comunidad de Madrid (grant numbers S-2010/BMD-2351 and S-2010/BMD-2332], CYTED 214RT0482, and R.C-R is supported by a grant of “Miguel Servet II” Program (CPII13/00033). CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008–2011, IniciativaIngenio 2010, the Consolider Program, and CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. Also, the authors thank Dr Maribel Clemente Mayoral for her technical assistance and advice as cell culture technician (CA10/01274). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.