PXD013306

PXD013306 is an original dataset announced via ProteomeXchange.

Title	An open-format enteroid culture system for interrogation of interactions between Toxoplasma gondii and the intestinal epithelium
Description	When transmitted through the oral route, Toxoplasma gondii first interacts with its host at the small intestinal epithelium. This interaction is crucial to controlling initial invasion and replication, as well as shaping the quality of the systemic immune response. It is therefore an attractive target for the design of novel vaccines and adjuvants. However, due to a lack of tractable infection models, we understand surprisingly little about the molecular pathways that govern this interaction. The in vitro culture of small intestinal epithelium as host-pathogen intreaction shows great promise for modelling the epithelial response to infection. However, the enclosed luminal space makes the application of infectious agents to the apical epithelial surface challenging. Here, we have developed three novel enteroid-based techniques for modelling T. gondii infection. In particular, we have adapted enteroid culture protocols to generate collagen-supported epithelial sheets with an exposed apical surface. These cultures retain epithelial polarization, and the presence of fully differentiated epithelial cell populations. They are susceptible to infection with, and support replication of, T. gondii. Using quantitative label-free mass spectrometry, we show that T. gondii infection of the enteroid epithelium is associated with up-regulation of proteins associated with cholesterol metabolism, extracellular exosomes, intermicrovillar adhesion, and cell junctions. Inhibition of host cholesterol and isoprenoid biosynthesis with Atorvastatin resulted in a dramatic reduction in parasite replication. These novel models therefore offer tractable tools for investigating how interactions between T. gondii and the host intestinal epithelium influence the course of infection.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_03:58:56.484.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stuart Armstrong
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Toxoplasma gondii; NCBI TaxID: NCBITaxon:5811;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-29 06:49:04	ID requested
1	2019-11-11 17:25:56	announced
⏵ 2	2024-10-22 03:58:57	announced	2024-10-22: Updated project metadata.

Luu L, Johnston LJ, Derricott H, Armstrong SD, Randle N, Hartley CS, Duckworth CA, Campbell BJ, Wastling JM, Coombes JL, and the Intestinal Epithelium. Front Cell Infect Microbiol, 9():300(2019) [pubmed]

10.3389/fcimb.2019.00300;

submitter keyword: Host-pathogen interaction,Toxoplasma gondii ,3D enteroids

Janine Coombes
contact affiliation	Department of Infection Biology Institute of Infection and Global Health University of Liverpool
contact email	J.Coombes@liverpool.ac.uk
lab head
Stuart Armstrong
contact affiliation	Infection Biology
contact email	sarmstro@liv.ac.uk
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/2019/11/PXD013306

PRIDE project URI

• PRIDE
  1. PXD013306
     1. Label: PRIDE project
     2. Name: An open-format enteroid culture system for interrogation of interactions between Toxoplasma gondii and the intestinal epithelium