Impact of Leishmania mexicana infection on dendritic cell signaling and functions

PLoS Negl Trop Dis. 2014 Sep 25;8(9):e3202. doi: 10.1371/journal.pntd.0003202. eCollection 2014 Sep.

Abstract

Leishmania parasites have the ability to modify macrophage signaling pathways in order to survive and multiply within its mammalian host. They are also known to invade other cells including neutrophils, fibroblasts and dendritic cells (DCs). DCs have an important role in immunity as the link between innate and adaptive immunity, necessary for the development of an effective response; however, the impact of Leishmania mexicana infection on DCs has been poorly studied. Herein, we report that Leishmania infection rapidly induced DC protein tyrosine phosphatases activity, leading to MAP kinases inactivation. In line with this, L. mexicana was found to decrease the nuclear translocation of transcription factors such as AP-1 and NF-κB. Concomitantly, L. mexicana-infected DCs showed reduced expression of several surface antigen-presenting and co-stimulatory molecules upon LPS stimulation. Leishmania-induced interference on DC maturation was further reflected by their reduced capacity to present OVA antigen to OVA-specific T cells, as shown by abrogation of IL-2 production by the T cells. Collectively, our data revealed that DC infection by L. mexicana appears to affect the cellular and immunological mechanisms necessary for the development of an effective and protective immune response, therefore favouring the survival and propagation of the parasite within its host.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-1 Antigen / immunology
  • B7-2 Antigen / immunology
  • CD40 Antigens / immunology
  • Cell Line
  • Dendritic Cells / enzymology
  • Dendritic Cells / immunology*
  • Dendritic Cells / parasitology*
  • Intercellular Adhesion Molecule-1 / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Leishmania mexicana / immunology*
  • Leishmaniasis / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • Protein Tyrosine Phosphatases / metabolism
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology

Substances

  • B7-1 Antigen
  • B7-2 Antigen
  • CD40 Antigens
  • Interleukin-2
  • Intercellular Adhesion Molecule-1
  • Mitogen-Activated Protein Kinases
  • Protein Tyrosine Phosphatases