PXD021844

PXD021844 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis of Brugia malayi microfilaria-derived extracellular vesicles
Description	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 and shown to be enriched (>2fold, 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 respectively. 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. 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.
HostingRepository	PRIDE
AnnounceDate	2021-01-12
AnnouncementXML	Submission_2021-01-11_23:49:59.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD021844
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Alessandra Ricciardi
SpeciesList	scientific name: Brugia malayi; NCBI TaxID: 6279;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-05 08:32:57	ID requested
⏵ 1	2021-01-11 23:49:59	announced

Ricciardi A, Bennuru S, Tariq S, Kaur S, Wu W, Elkahloun AG, Arakelyan A, Shaik J, Dorward DW, Nutman TB, Tolouei Semnani R, Extracellular vesicles released from the filarial parasite Brugia malayi downregulate the host mTOR pathway. PLoS Negl Trop Dis, 15(1):e0008884(2021) [pubmed]

submitter keyword: Extracelluar vesicles, Brugia malayi, microfilaria, LC-MSMS

Dr. Thomas Nutman
contact affiliation	Thomas B. Nutman, M.D. Chief, Laboratory of Parasitic Diseases Bldg 4 Room 211C 4 Center Dr. National Institutes of Health Bethesda, MD 20892-0425
contact email	tnutman@niaid.nih.gov
lab head
Alessandra Ricciardi
contact affiliation	National Institutes of Health NIAID
contact email	alessandra.ricciardi@nih.gov
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/01/PXD021844

PRIDE project URI

• PRIDE
  1. PXD021844
     1. Label: PRIDE project
     2. Name: Proteomic analysis of Brugia malayi microfilaria-derived extracellular vesicles