Immunostimulatory effects of Leishmania infantum HSP70 recombinant protein on dendritic cells in vitro and in vivo

Immunotherapy. 2014;6(5):577-85. doi: 10.2217/imt.14.28.

Abstract

Background: Activation of dendritic cells (DCs) has an important role in immunity against Leishmania.

Aim: We investigated the effect of Leishmania infantum (L. infantum) heat shock protein 70 recombinant protein (rHSP70) as a vaccine on DC maturation and function.

Materials & methods: BALB/c mouse splenic DCs were isolated and treated with different concentrations of rHSP70. Maturation markers, cytokine production and capability of DCs to proliferate allogeneic T cells were evaluated. Furthermore, this recombinant protein was injected into BALB/c mice, and expression of CD86, CD40 and MHC class II molecules by their splenic DCs were evaluated.

Results: rHSP70 significantly increases the production of IL-12p70 by DCs. It had no effect on allogeneic T-cell proliferation in mixed lymphocyte reaction. It increased IFN-γ and decreased IL-4 cytokine level in mixed lymphocyte reaction supernatant. The in vitro study showed that rHSP70 had no significant effect neither on the percentage of CD40(+), CD86(+) and MHC class II(+) DCs nor on the mean fluorescent intensity. However, in vivo results showed that rHSP70 increases the percentage of CD86-, CD40- and MHC class II-expressing cells as well as mean fluorescent intensity of CD40 and MHC class II.

Conclusion: This study demonstrated the capability of L. infantum-derived rHSP70 in maturating BALB/c mice splenic DCs and in vivo polarization of immunity to a Th1 response.

Keywords: Leishmania infantum; dendritic cell; heat shock protein 70; immunostimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • B7-2 Antigen / immunology
  • CD40 Antigens / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Female
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / immunology
  • HSP70 Heat-Shock Proteins / pharmacology*
  • Histocompatibility Antigens Class II / immunology
  • Interleukin-12 / immunology
  • Interleukin-4 / immunology
  • Leishmania infantum / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology
  • Protozoan Proteins / pharmacology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology

Substances

  • Adjuvants, Immunologic
  • B7-2 Antigen
  • CD40 Antigens
  • Cd86 protein, mouse
  • HSP70 Heat-Shock Proteins
  • Histocompatibility Antigens Class II
  • Protozoan Proteins
  • Recombinant Proteins
  • Interleukin-12
  • Interleukin-4