Plant-Based Alternative Treatment for Leishmaniasis: A Neglected Tropical Disease

Leishmaniasis is a third most important vector born disease caused by intracellular parasite belongs to genus Leishmania. The leishmaniasis is prevalent in 102 countries/areas worldwide. Approximately, it effected 350 million people worldwide. Leishmaniasis effects developing and undeveloped countries globally. Antileishmanial drugs (pentavalent antimonials, stibogluconate, miltefosine, paramycin, and amphotericin) are most vital tool for curing leishmaniasis. However, none of these drugs is free from side effect including cost, toxicity, drug resistance, administration route, and prolong time, these disadvantages are main obstacle in the Leishmania infection eradication. Considering the increasing cases of leishmaniasis and drug resistance there is an urgent need for an effective and novel approach against leishmaniasis. Therefore, many researchers have tried to develop new medicines for the treatment of Leishmania infection. In the course of new therapies identification, plant based compounds were found to be an alternative that can be either used directly or with structural modifications. Several plants have been known for ages to be the source of phytochemicals with high values of medicines. These phytochemicals have been extracted by various techniques and have shown efficacy for the curing of several diseases. This chapter study explain various applications based on green approaches drugs for the treatment of leishmaniasis

Dual-scRNA-seq analysis reveals rare and uncommon parasitized cell populations in chronic L. donovani infection

Summary: Although phagocytic cells are documented targets of Leishmania parasites, it is unclear whether other cell types can be infected. Here, we use unbiased single-cell RNA sequencing (scRNA-seq) to simultaneously analyze host cell and Leishmania donovani transcriptomes to identify and annotate parasitized cells in spleen and bone marrow in chronically infected mice. Our dual-scRNA-seq methodology allows the detection of heterogeneous parasitized populations. In the spleen, monocytes and macrophages are the dominant parasitized cells, while megakaryocytes, basophils, and natural killer (NK) cells are found to be unexpectedly infected. In the bone marrow, the hematopoietic stem cells (HSCs) expressing phagocytic receptors FcγR and CD93 are the main parasitized cells. Additionally, we also detect parasitized cycling basal cells, eosinophils, and macrophages in chronically infected mice. Flow cytometric analysis confirms the presence of parasitized HSCs. Our unbiased dual-scRNA-seq method identifies rare, parasitized cells, potentially implicated in pathogenesis, persistence, and protective immunity, using a non-targeted approach

Immunological alterations in tuberculosis associated immune reconstitution inflammatory syndrome in HIV infected patients

786-795The tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) frequently complicates the course of HIV/AIDS and HIV-TB treatment and its immunological mechanisms are poorly understood. Here, we investigated T-cells frequencies, their secreted chemokines and cytokines. In this prospective case-control study, HIV/AIDS and HIV-TB patients during treatment with highly active antiretroviral treatment (HAART) and anti-TB treatment were followed for TB-IRIS development. Age, gender and BMI-matched patients without IRIS constituted as “Controls” (non-IRIS). Activation and proliferation were assessed in CD4 and CD8 cell compartments. CCR4, CCR6 and T-reg cells were also analysed in PBMCs. Cytokines (IL-2, IL-4, IL-10, IFN-γ and TGF-β1) and chemokines (IP-10, MCP-1, MIG and RANTES) were measured in culture supernatants. Of 560 enrolled HIV/AIDS patients, TB-IRIS developed in 50 (8.9%) patients (25-paradoxical and 25-unmasking) at a median interval of 35-days (IQR, 24-78). After ART therapy, CD8+ T-cell proportion decreased in both paradoxical and unmasking-TB-IRIS as compared to non-IRIS. Simultaneously, activation of CD4+ T-cells was observed in unmasking TB-IRIS only. Similarly, CD161+ T-cells, Th17-cells and inflammatory cytokines like IFN-γ, IP-10 and MIG elevated in both TB-IRIS subgroups as compared to non-IRIS.In conclusion, during HAART treatment the dominance of pro-inflammatory cells and cytokines in TB-IRIS patients favours the development of IRIS event. On the other hand, in non-IRIS patients relative increase of anti-inflammatory cells and cytokines prevents the development of IRIS event

Immunization with a Trypanosoma cruzi cyclophilin-19 deletion mutant protects against acute Chagas disease in mice

Abstract Human infection with the protozoan parasite Trypanosoma cruzi causes Chagas disease for which there are no prophylactic vaccines. Cyclophilin 19 is a secreted cis-trans peptidyl isomerase expressed in all life stages of Trypanosoma cruzi. This protein in the insect stage leads to the inactivation of insect anti-parasitic peptides and parasite transformation whereas in the intracellular amastigotes it participates in generating ROS promoting the growth of parasites. We have generated a parasite mutant with depleted expression of Cyp19 by removal of 2 of 3 genes encoding this protein using double allelic homologous recombination. The mutant parasite line failed to replicate when inoculated into host cells in vitro or in mice indicating that Cyp19 is critical for infectivity. The mutant parasite line also fails to replicate in or cause clinical disease in immuno-deficient mice further validating their lack of virulence. Repeated inoculation of mutant parasites into immuno-competent mice elicits parasite-specific trypanolytic antibodies and a Th-1 biased immune response and challenge of mutant immunized mice with virulent wild-type parasites is 100% effective at preventing death from acute disease. These results suggest that parasite Cyp19 may be candidate for small molecule drug targeting and that the mutant parasite line may warrant further immunization studies for prevention of Chagas disease