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

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.

Investigating the Existence of Ribosomal Protein L5 Gene in Syrian Strain of Leishmania tropica Genome: Sequencing It and Evaluating Its Immune Response as DNA Vaccine

“…The pCI-L5 vaccine was able to induce partial protection against infection with Leishmania tropica, and the ratio of IFN-γ/IL-4 in the draining lymph nodes (DLNs) of mice of the study group was 2.83 and 3.62 at the second and fourth weeks after the challenge, respectively, and then it stabilized at the value of 5.07 at the sixth week (greater than 1). Therefore, the cell-mediated immune response caused by the vaccine after two weeks was the TH1 type since the ratio of IFN-γ/IL-4 was greater than 1, and this ratio was sufficient to induce partial immunity against Leishmania tropica, which is associated with a decrease in the size of the lesion as discussed by Masoudzadeh et al [30] and the survival of fewer parasites in the lesions and in the draining lymph nodes after the sixth week of the challenge.…”

“…Some studies demonstrated that certain strains of L. tropica cause mild pathogenesis in BALB/c mice characterized by small or no detectable swelling in the injection site, so measuring lesion size was not considered as a promising tool for the evaluation of vaccine efficiency as discussed by Fate-meh et al [17] and Rostamian et al [29]. In fact, in some cases, cutaneous lesions due to L. tropica may develop to ulcerative detectable lesions as discussed by Masoudzadeh et al [30], like the case in our study, so monitoring lesion size could strongly reflect the immune response obtained from the vaccines used.…”

A 92 protein inflammation panel performed on sonicate fluid differentiates periprosthetic joint infection from non-infectious causes of arthroplasty failure

“…1) 35 . Recently, the panel has been utilized to characterize the inflammatory response during infectious diseases, including leishmaniasis, tuberculosis, urinary tract, HIV, and COVID-19 [36][37][38][39][40] . The panel has also been used to investigate musculoskeletal inflammation during rheumatoid arthritis and in a porcine model of S. aureus bone infection [41][42][43] .…”

Advances in Understanding Leishmania Pathobiology: What Does RNA-Seq Tell Us?

“…Global RNA-Seq and transcriptome analysis has gained significant attention as a tool to unveil Leishmania species molecular biology and their pathogenicity, differentiation into various life stages and interplay with the host immune response ( Dillon et al, 2015b ; Shadab et al, 2019 ). The simultaneous analysis of the gene expression profiles of parasites and hosts is a critical step in our understanding of the disease ( Dillon et al, 2015b ; Masoudzadeh et al, 2020b ). However, with the colossal amount of data generated, there is a need to “translate” these complex datasets into forms that can be exploited for drug and vaccine development.…”