ArticlePLoS neglected tropical diseases2021
Extracellular vesicles released from the filarial parasite Brugia malayi downregulate the host mTOR pathway.
Article in PLoS neglected tropical diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Lack of detectable short-term effects of a single dose of ivermectin on the human immune system.Parasites & vectors · 2021Trial
- Unraveling the Dynamics of Human Filarial Infections: Immunological Responses, Host Manifestations, and Pathogen Biology.Pathogens (Basel, Switzerland) · 2025Review
- Article
- The expanding role of microRNAs in the biology and control of veterinary parasitic nematodes.Frontiers in veterinary science · 2025Review
- Unraveling the microRNAs Involved in Fasciolosis: Master Regulators of the Host-Parasite Crosstalk.International journal of molecular sciences · 2024Review
- Anisakis extracellular vesicles elicit immunomodulatory and potentially tumorigenic outcomes on human intestinal organoids.Parasites & vectors · 2024Article
- Alterations of plasma circulating microRNAs in BALB/c mice with Toxocara canis visceral and cerebral larva migrans.Parasites & vectors · 2024Article
- Host innate immune systems gather intel on invading microbes via pathogen-derived extracellular vesicles.Extracellular vesicle · 2024Article
- Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS-induced colitis in a murine model.Journal of extracellular vesicles · 2024Article
- Exploring extracellular vesicles in zoonotic helminth biology: implications for diagnosis, therapeutic and delivery.Frontiers in cellular and infection microbiology · 2024Review
- Overview of extracellular vesicles in pathogens with special focus on human extracellular protozoan parasites.Memorias do Instituto Oswaldo Cruz · 2024Review
- Roles of helminth extracellular vesicle-derived let-7 in host-parasite crosstalk.Frontiers in immunology · 2024Review
- Article
- Extracellular vesicles secreted by Brugia malayi microfilariae modulate the melanization pathway in the mosquito host.Scientific reports · 2023Article
- Identification of biomarker candidates for filarial parasite infections by analysis of extracellular vesicles.Frontiers in parasitology · 2023Article
- How to train your myeloid cells: a way forward for helminth vaccines?Frontiers in immunology · 2023Review
- microRNAs: Critical Players during Helminth Infections.Microorganisms · 2022Review
- Inflammatory Response in Caco-2 Cells Stimulated withPathogens (Basel, Switzerland) · 2022Article
- Whipworm secretions and their roles in host-parasite interactions.Parasites & vectors · 2022Review
- Emerging Roles of Micrornas in Veterinary Cardiology.Veterinary sciences · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
We have previously shown that the microfilarial (mf) stage of Brugia malayi can inhibit the mammalian target of rapamycin (mTOR; a conserved serine/threonine kinase critical for immune regulation and cellular growth) in human dendritic cells (DC) and we have proposed that this mTOR inhibition is associated with the DC dysfunction seen in filarial infections. Extracellular vesicles (EVs) contain many proteins and nucleic acids including microRNAs (miRNAs) that might affect a variety of intracellular pathways. Thus, EVs secreted from mf may elucidate the mechanism by which the parasite is able to modulate the host immune response during infection. EVs, purified from mf of Brugia malayi and confirmed by size through nanoparticle tracking analysis, were assessed by miRNA microarrays (accession number GSE157226) and shown to be enriched (>2-fold, p-value<0.05, FDR = 0.05) for miR100, miR71, miR34, and miR7. The microarray analysis compared mf-derived EVs and mf supernatant. After confirming their presence in EVs using qPCR for these miRNA targets, web-based target predictions (using MIRPathv3, TarBAse and MicroT-CD) predicted that miR100 targeted mTOR and its downstream regulatory protein 4E-BP1. Our previous data with live parasites demonstrated that mf downregulate the phosphorylation of mTOR and its downstream effectors. Additionally, our proteomic analysis of the mf-derived EVs revealed the presence of proteins commonly found in these vesicles (data are available via ProteomeXchange with identifier PXD021844). We confirmed internalization of mf-derived EVs by human DCs and monocytes using confocal microscopy and flow cytometry, and further demonstrated through flow cytometry, that mf-derived EVs downregulate the phosphorylation of mTOR in human monocytes (THP-1 cells) to the same degree that rapamycin (a known mTOR inhibitor) does. Our data collectively suggest that mf release EVs that interact with host cells, such as DC, to modulate host responses.
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