The role of 'omics' in the quest to eliminate human filariasis

Lustigman, Sara; Grote, Alexandra; Ghedin, Elodie

doi:10.1371/journal.pntd.0005464

Cited by 15 publications

(15 citation statements)

References 83 publications

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“…The release of such a protected package can undoubtedly optimize the integrity of contents, which in turn improve their efficacy in genetic exchange and secure delivery to modulate host immunity ( 203 ). Indeed, several studies have shown that powerful biomolecules are present in the helminth-derived EVs, which can offer potential and druggable candidates against inflammatory diseases ( 204 ). In addition, omics-based approaches, such as proteomics and transcriptomics have provided a plethora of valuable data facilitating recognition of major components mediating host immunosuppression.…”

Section: Evs For the Host Immune Systemmentioning

confidence: 99%

Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles

et al. 2018

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Helminth parasites are masters at manipulating host immune responses, using an array of sophisticated mechanisms. One of the major mechanisms enabling helminths to establish chronic infections is the targeting of pattern recognition receptors (PRRs) including toll-like receptors, C-type lectin receptors, and the inflammasome. Given the critical role of these receptors and their intracellular pathways in regulating innate inflammatory responses, and also directing adaptive immunity toward Th1 and Th2 responses, recognition of the pathways triggered and/or modulated by helminths and their products will provide detailed insights about how helminths are able to establish an immunoregulatory environment. However, helminths also target PRRs-independent mechanisms (and most likely other yet unknown mechanisms and pathways) underpinning the battery of different molecules helminths produce. Herein, the current knowledge on intracellular pathways in antigen presenting cells activated by helminth-derived biomolecules is reviewed. Furthermore, we discuss the importance of helminth-derived vesicles as a less-appreciated components released during infection, their role in activating these host intracellular pathways, and their implication in the development of new therapeutic approaches for inflammatory diseases and the possibility of designing a new generation of vaccines.

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Section: Evs For the Host Immune Systemmentioning

confidence: 99%

Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles

et al. 2018

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“…Moreover, these drugs are also associated with other complications like toxicity, undesirable drug interactions and emergence of drug resistance. [3][4][5] Thus, identification of new class of drug with novel mode of action is highly desirable.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Structure Elucidation, Homology Modeling and Antifilarial Activity of 7‐Benzamidocoumarin Derivatives

et al. 2019

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A series of 7‐benzamidocoumarin derivatives 10–25 starting from 7‐amino coumarins 7 and 8 has been synthesized, characterized and evaluated in vitro for antifilarial activity against the human lymphatic filarial parasite, Brugia malayi. Compounds 13 and 20–23 showed permanent paralysis of the worm with 90–95% inhibition of motility of adult worms at 10 μM. All the synthesized compounds were docked on the modeled receptor of Onchocerca volvulus chitinase OvCHT1. Compound 13 with binding energy of −7.95 Kcal/mol showing three hydrogen bonds with the active site of the enzyme emerged as the best inhibitor.

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“…In related studies, a central repository of genes from C . elegans and other free-living and parasitic nematodes has been curated into a WormBase for comparative genomics [ 15 , 16 ], while new functional tools such as RNAi, transgenesis, and CRISPR/Cas genome disruption and editing are revealing new information about human parasites, including new targets for intervention [ 17 , 18 ]. Genome editing has also been proposed as an approach toward producing attenuated parasites for functional studies or for vaccine development [ 19 ].…”

Section: Functional and Comparative Omics And Gene Editingmentioning

confidence: 99%

The poverty-related neglected diseases: Why basic research matters

Hotez

2017

PLoS Biol

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Together, malaria and the neglected tropical diseases (NTDs) kill more than 800,000 people annually, while creating long-term disability in millions more. International support for mass drug administration, bed nets, and other preventive measures has resulted in huge public health gains, while support for translational research is leading to the development of some new neglected disease drugs, diagnostics, and vaccines. However, funding for basic science research has not kept up, such that we are missing opportunities to create a more innovative pipeline of control tools for parasitic and related diseases. There is an urgent need to expand basic science approaches for neglected diseases, especially in the areas of systems biology and immunology; ecology, evolution, and mathematical biology; functional and comparative OMICs; gene editing; expanded use of model organisms; and a new single-cell combinatorial indexing RNA sequencing approach. The world’s poor deserve access to innovation for neglected diseases. It should be considered a fundamental human right.

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The role of 'omics' in the quest to eliminate human filariasis

Cited by 15 publications

References 83 publications

Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles

Immunomodulation by Helminths: Intracellular Pathways and Extracellular Vesicles

Synthesis, Structure Elucidation, Homology Modeling and Antifilarial Activity of 7‐Benzamidocoumarin Derivatives

The poverty-related neglected diseases: Why basic research matters

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