Project description:Visceral leishmaniasis (VL) in Sudan caused by Leishmania donovani is fatal in susceptible individuals if untreated. Treatment with Sodium Stibogluconate (SSG) leads to post kala azar dermal leishmaniasis (PKDL) in 58% of patients. Here Affymetrix microarrays were used to identify genes differentially expressed in lymph nodes (N=9 paired samples) pre- and post-treatment with SSG. Using the Bioconductor package limma, 438 genes from 28,869 post quality-control probe-sets were differentially expressed (Pnominal≤0.02) post- versus pre-treatment. Canonical pathway analysis using Ingenuity Pathway Analysis identified “Role of NFAT in Regulation of Immune Response” (Pnominal=1.35x10-5; PBH-adjusted=4.79x10-3), “B Cell Development” (Pnominal=2.04x10-4; PBH-adjusted=0.024), “Fcγ Receptor-mediated Phagocytosis in Macrophages and Monocytes” (Pnominal=2.04x10-4; PBH-adjusted=0.024), and “OX40 Signaling” (Pnominal=2.82x10-4; PBH-adjusted=0.025) as pathways differentially regulated post- versus pre-treatment. Major network hub genes included TP53, FN1, MYC, BCL2, JUN, SYK, RUNX2, MMP1 and ACTA2. Top endogenous upstream regulators included IL-7 (P=2.28x10-6), TNF (P=4.26x10-6), APP (P=4.23x10-5) and SPI1/PI.1 (P=1.17x10-7). Top predicted chemical drug regulators included the flavonoid genistein (P=4.56x10-7) and the quinoline alkaloid camptothecin (P=5.14x10-5). These results contribute to our understanding of immuno-pathology associated with VL and response to SSG treatment. Further replication could identify novel therapeutic strategies that improve on SSG treatment and reduce the likelihood of progression to PKDL.
Project description:Whole blood transcriptomes taken from patients with cutaneous leishmaniasis at presentation and during sodium stibogluconate treatment.
Project description:As a vector-borne disease, leishmaniasis is caused by a parasitic protozoans of leishmania genus and transmitted by female Phlebotomine sandflies. Depending on the body location where immotile form of the parasite namely amastigote is proliferated, three main clinical forms as cutaneous, muco-cutaneous and visceral leishmaniases are defined. While manifestation of cutaneous leishmaniasis is skin lesions on the exposed part of the body, enlarged lymph nodes, spleen or liver along with fever, fatigue and weight loss are the symptoms of visceral leishmaniasis. The most dangerous form is visceral leishmaniasis since it may end up with fatalities if patients are not treated. The purpose of this study was to investigate the difference between the protein expression profiles of leishmania isolates obtained from visceral and cutaneous leishmaniasis patients. To compare two sample groups to each other genetically, L.infantum was chosen since it causes both visceral and cutaneous leishmaniasis. Additionally, another sample group as cutaneous leishmaniasis caused by L.tropica was included to make the comparison both intra- and interspecies level. For protein profiling, both gel-based and gel-free proteomic approaches were carried out. In brief, a total of 15 samples, 5 from each group, were separated on pI 3-10 2D-PAGE gel. Additionally, 9 of those 15 samples, 3 from each group, were analyzed according to qualitative shotgun proteomics method and differential proteins were determined by drawing venn diagram.
Project description:Leishmaniasis affects mainly the poorest population of the third world. Among visceral and cutaneous leishmaniasis (VL and CL, respectively), visceral leishmaniasis is the deadliest parasitic disease. There are no vaccines against leishmaniasis and the chemotherapeutic agents currently used are also insufficient. Pentavalent antimonials are being used for the effective treatment of Leishmaniasis. In this study, we characterized compounds with leishmanicidal activity, and determined its mode of action through the whole transcriptome analyiss. The Lesihmania strains were treated with previously identified selected anti-leishmanial compounds in promastigotes cultures on M199 medium (supplemented with L-glutamine, 10% heat-inactivated fetal bovine serum, 0.25% hemin, 40 mM NaHCO3, 100μM adenine, 40 mM HEPES, 100 U/mL penicillin and 100μg/mL streptomycin). Following the total RNA isolation, RNA-seq was performed using the Illumina NextSeq500 system. The genes expression profiling in the treated and control samples were determined using the standard bioinormatics tools, and then compared statistically.
Project description:Gene expression profiling to address the effects of infection with Leishmania infantum during distinct clinical outcomes as active visceral leishmaniasis (VL), remission of disease and asymptomatic infection. Total RNA was extracted from whole-blood lysates obtained from VL patients, treated VL patients, asymptomatic individuals and uninfected controls. The aim was to evaluate gene expression signatures associated with protective and pathological responses.
Project description:This study was designed to invesitgate changes in the transcriptional changes in CD4+ T cells from visceral leishmaniasis patients infected with L. donovani.
Project description:Gene expression profiling to address the effects of infection with Leishmania infantum during distinct clinical outcomes as active visceral leishmaniasis (VL), remission of disease and asymptomatic infection.
Project description:To ascertain which genes are involved in pathogenesis of human visceral leishmaniasis (VL) caused by the protozoan parasite Leishmania infantum, we investigated the transcriptional profile of whole blood samples from patients diagnosed with active VL compared to healthy control samples.