Abstract

Anthroponotic cutaneous leishmaniasis (CL) caused by Leishmania tropica (L. tropica) represents a public health challenge in several resource poor settings. We herein employed a systems analysis approach to study molecular signatures of CL caused by L. tropica in the skin lesions of ulcerative CL (UCL) and non-ulcerative CL (NUCL) patients. Results from RNA-seq analysis determined shared and unique functional transcriptional pathways in the lesions of the UCL and NUCL patients. Several transcriptional pathways involved in inflammatory response were positively enriched in the CL lesions. A multiplexed inflammatory protein analysis showed differential profiles of inflammatory cytokines and chemokines in the UCL and NUCL lesions. Transcriptional pathways for Fcγ receptor dependent phagocytosis were among shared enriched pathways. Using L. tropica specific antibody (Ab)-mediated phagocytosis assays, we could substantiate Ab-dependent cellular phagocytosis (ADCP) and Ab-dependent neutrophil phagocytosis (ADNP) activities in the lesions of the UCL and NUCL patients, which correlated with L. tropica specific IgG Abs. Interestingly, a negative correlation was observed between parasite load and L. tropica specific IgG/ADCP/ADNP in the skin lesions of CL patients. These results enhance our understanding of human skin response to CL caused by L. tropica.

Details

Title
Molecular signatures of anthroponotic cutaneous leishmaniasis in the lesions of patients infected with Leishmania tropica
Author
Masoudzadeh Nasrin 1 ; Östensson Malin 2 ; Persson Josefine 2 ; Mashayekhi, Goyonlo Vahid 3 ; Agbajogu Christopher 2 ; Taslimi Yasaman 1 ; Erfanian, Salim Reza 4 ; Zahedifard Farnaz 1 ; Mizbani Amir 5 ; Malekafzali Ardekani Housein 1 ; Gunn, Bronwyn M 6 ; Rafati Sima 1 ; Harandi, Ali M 7 

 Pasteur Institute of Iran, Department of Immunotherapy and Leishmania Vaccine Research, Tehran, Iran (GRID:grid.420169.8) (ISNI:0000 0000 9562 2611) 
 Sahlgrenska Academy, University of Gothenburg, Department of Microbiology and Immunology, Institute of Biomedicine, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582) 
 Mashhad University of Medical Sciences, Cutaneous Leishmaniasis Research Center, Mashhad, Iran (GRID:grid.411583.a) (ISNI:0000 0001 2198 6209) 
 Noor Eye Hospital, Tehran, Iran (GRID:grid.416362.4) (ISNI:0000 0004 0456 5893) 
 ETH Zurich, Zurich, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780) 
 Ragon Institute of MGH, MIT, and Harvard University, Cambridge, USA (GRID:grid.420169.8); Washington State University, Paul G. Allen School of Global Animal Health, Pullman, USA (GRID:grid.30064.31) (ISNI:0000 0001 2157 6568) 
 Sahlgrenska Academy, University of Gothenburg, Department of Microbiology and Immunology, Institute of Biomedicine, Gothenburg, Sweden (GRID:grid.8761.8) (ISNI:0000 0000 9919 9582); The University of British Columbia, Vaccine Evaluation Center, BC Children’s Hospital Research Institute, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2449454044
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.