Molecular signatures of anthroponotic cutaneous leishmaniasis in the lesions of patients infected with Leishmania tropica

Nasrin Masoudzadeh,Christopher Agbajogu,Sima Rafati,Yasaman Taslimi,Farnaz Zahedifard,Bronwyn M Gunn,Housein Malekafzali Ardekani,Amir Mizbani,Malin Östensson,Vahid Mashayekhi Goyonlo,Ali M Harandi,Reza Erfanian Salim,Josefine Persson

doi:10.1038/s41598-020-72671-7

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.

Highlights

Anthroponotic cutaneous leishmaniasis (CL) caused by Leishmania tropica (L. tropica) represents a public health challenge in several resource poor settings
Using a non-invasive sampling method combined with L. tropica specific PCR23, all CL patients were diagnosed as L. tropica positive (Fig. S1)
We applied whole genome RNA sequencing along with high-throughput PEA assay and antibody-dependent phagocytosis assays combined with systems biology approaches to pinpoint molecular signatures of human response to L. tropica infection in the lesions of ulcerative CL (UCL) and non-ulcerative CL (NUCL) patients

Summary

Introduction

Anthroponotic cutaneous leishmaniasis (CL) caused by Leishmania tropica (L. tropica) represents a public health challenge in several resource poor settings. We 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. 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. Anthroponotic CL (ACL), caused by L. tropica, and zoonotic CL (ZCL), caused by L. major, are two pre-dominant variants of CL that are highly prevalent in the endemic countries and represent a major health problem in the Old W orld[5,6]. Cutaneous lesions caused by L. tropica are characterized by papules and nodules (non-ulcerative CL; NUCL), which in some cases may develop progressively to an ulcerative form A limited number of human studies have focused on understanding immune mechanisms involved in L. tropica-induced CL9,16,17

Methods

Results

Conclusion