ArticlePLoS neglected tropical diseases2016
Live Attenuated Leishmania donovani Centrin Knock Out Parasites Generate Non-inferior Protective Immune Response in Aged Mice against Visceral Leishmaniasis.
Article in PLoS neglected tropical diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Mechanistic insights into LdCen1-LdDRP interaction facilitating UV-induced DNA damage repair in Leishmania donovani.Medical microbiology and immunology · 2025Article
- An Update on Clinical and Pathogenic Spectra of Leishmaniasis.Expert reviews in molecular medicine · 2025Review
- Design, synthesis and biological activity of peptidyl β-nitrostyrenes as cysteine protease inhibitors againstRSC advances · 2025Article
- An update on recombinant vaccines against leishmaniasis.The Indian journal of medical research · 2024Review
- Manufacturing and preclinical toxicity of GLP grade gene deleted attenuated Leishmania donovani parasite vaccine.Scientific reports · 2024Article
- Live attenuated-nonpathogenicFrontiers in microbiology · 2024Review
- Deletion of MIF gene from live attenuated LdCenScientific reports · 2023Article
- Next-Generation Leishmanization: Revisiting Molecular Targets for Selecting Genetically Engineered Live-AttenuatedMicroorganisms · 2023Review
- Article
- The History of Live AttenuatedPathogens (Basel, Switzerland) · 2022Review
- Systematic identification of genes encoding cell surface and secreted proteins that are essential for in vitro growth and infection in Leishmania donovani.PLoS pathogens · 2022Article
- Selection of antileishmanial sesquiterpene lactones from SistematX database using a combined ligand-/structure-based virtual screening approach.Molecular diversity · 2021Article
- Characterization of a new Leishmania major strain for use in a controlled human infection model.Nature communications · 2021Article
- Targeted Deletion of Centrin inFrontiers in cellular and infection microbiology · 2021Article
- miR-21 Expression Determines the Early Vaccine Immunity Induced byFrontiers in immunology · 2019Article
- Growth arrested live-attenuated Leishmania infantum KHARON1 null mutants display cytokinesis defect and protective immunity in mice.Scientific reports · 2018Article
- Centrin-DeletedFrontiers in immunology · 2018Article
- Translational Rodent Models for Research on Parasitic Protozoa-A Review of Confounders and Possibilities.Frontiers in cellular and infection microbiology · 2017Review
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVisceral leishmaniasis (VL) caused by the protozoan parasite Leishmania donovani causes severe disease. Age appears to be critical in determining the clinical outcome of VL and at present there is no effective vaccine available against VL for any age group. Previously, we showed that genetically modified live attenuated L. donovani parasites (LdCen-/-) induced a strong protective innate and adaptive immune response in young mice. In this study we analyzed LdCen-/- parasite mediated modulation of innate and adaptive immune response in aged mice (18 months) and compared to young (2 months) mice. METHODOLOGY: Analysis of innate immune response in bone marrow derived dendritic cells (BMDCs) from both young and aged mice upon infection with LdCen-/- parasites, showed significant enhancement of innate effector responses, which consequently augmented CD4+ Th1 cell effector function compared to LdWT infected BMDCs in vitro. Similarly, parasitized splenic dendritic cells from LdCen-/- infected young and aged mice also revealed induction of proinflammatory cytokines (IL-12, IL-6, IFN-γ and TNF) and subsequent down regulation of anti-inflammatory cytokine (IL-10) genes compared to LdWT infected mice. We also evaluated in vivo protection of the LdCen-/- immunized young and aged mice against virulent L. donovani challenge. Immunization with LdCen-/- induced higher IgG2a antibodies, lymphoproliferative response, pro- and anti-inflammatory cytokine responses and stimulated splenocytes for heightened leishmanicidal activity associated with nitric oxide production in young and aged mice. Furthermore, upon virulent L. donovani challenge, LdCen-/- immunized mice from both age groups displayed multifunctional Th1-type CD4 and cytotoxic CD8 T cells correlating to a significantly reduced parasite burden in the spleen and liver compared to naïve mice. It is interesting to note that even though there was no difference in the LdCen-/- induced innate response in dendritic cells between aged and young mice; the adaptive response specifically in terms of T cell and B cell activation in aged animals was reduced compared to young mice which correlated with less protection in old mice compared to young mice.
conclusionsTaken together, LdCen-/- immunization induced a significant but diminished host protective response in aged mice after challenge with virulent L. donovani parasites compared to young mice.
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