Comparative Proteomic Analysis of Murine Cutaneous Lesions Induced by Leishmania amazonensis or Leishmania major

ACS Infect Dis. 2019 Aug 9;5(8):1295-1305. doi: 10.1021/acsinfecdis.8b00370. Epub 2019 May 29.

Abstract

Cutaneous leishmaniasisis is the most common clinical form of leishmaniasis and one of the most relevant neglected diseases. It is known that the progress of the disease is species specific and the host's immune response plays an important role in its outcome. However, the pathways that lead to parasite clearance or survival remain unknown. In this work, skin tissue from mice experimentally infected with L. amazonensis, one of the causative agents of cutaneous leishmaniasis in the Amazon region, L. major, another causative agent of cutaneous leishmaniasis in Africa, the Middle East, China, and India, or lipopolysaccharides from Escherichia coli as an inflammation model were investigated using label-free proteomics to unveil Leishmania-specific protein alterations. Proteomics is a powerful tool to investigate host-pathogen relationships to address biological questions. In this work, proteins from mice skin biopsies were identified and quantified using nano-LC coupled with tandem mass spectrometry analyses. Integrated Proteomics Pipeline was used for peptide/protein identification and quantification. Western blot was used for validation of protein quantification by mass spectrometry, and protein pathways were predicted using Ingenuity Pathway Analysis. In this proteomics study, several proteins were pointed out as hypothetical targets to guide future studies on Leishmania-specific modulation of proteins in the host. We identified hundreds of exclusively modulated proteins after Leishmania spp. infection and 17 proteins that were differentially modulated in the host after L. amazonensis or L. major infection.

Keywords: cutaneous leishmaniasis; host−pathogen interaction; label-free proteomics; mass spectrometry.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biopsy
  • Female
  • Host-Pathogen Interactions*
  • Inflammation
  • Leishmania braziliensis / pathogenicity*
  • Leishmania major / pathogenicity*
  • Leishmaniasis, Cutaneous / metabolism*
  • Leishmaniasis, Cutaneous / pathology
  • Mice
  • Mice, Inbred BALB C
  • Protein Interaction Maps
  • Proteins / analysis
  • Proteomics*
  • Skin / metabolism*
  • Skin / parasitology
  • Skin / pathology
  • Tandem Mass Spectrometry

Substances

  • Proteins