PXD041957

PXD041957 is an original dataset announced via ProteomeXchange.

Title	Cathelicidin deficiency disrupts goblet cell mucus secretion but not mucus associated proteins in Citrobacter rodentium-induced colitis
Description	Colonic goblet cells respond to invading enteropathogens by secreting Muc2 mucin and other specific goblet cell proteins that physically entrap and expel microbes away from the epithelium. At present, it is unclear how innate effectors in the gut, including small cationic cathelicidin peptides secreted by the intestinal epithelium and leukocytes, contribute to mucus barrier defense during infections. In this study, we used cathelicidin-deficient (Camp-/-) mice, colonoids, and human colonic LS174T goblet cells to elucidate the mechanisms by which cathelicidin regulates goblet cell secretions in innate host defense against attaching/effacing Citrobacter rodentium. We showed that even though Camp-/- littermates infected with C. rodentium displayed increased fecal shedding and epithelial colonization, Muc2 mucin granules were retained in bloated colonic goblet cells that impaired mucus secretion and expressed less mucus-associated proteins, as quantified by proteomic analysis. C. rodentium infected Camp-/- littermates showed impaired reactive oxygen species (ROS) production and transcriptomic profiling associated with decreased ROS biosynthesis and an increase in ROS negative regulators. Camp-/- bone marrow derived macrophages produced less ROS than their wild-type counterparts. In LS174T goblet cells, human cathelicidin LL-37 promptly induced the secretion of goblet cell-associated TFF3 and RELMβ, which was dependent on ROS production. These findings demonstrate that cathelicidin signaling in colonic goblet cells regulates mucus and mucin-associated protein secretion via an ROS-dependent mechanism to clear bacterial infections and restore gut homeostasis.
HostingRepository	PRIDE
AnnounceDate	2023-05-04
AnnouncementXML	Submission_2023-05-03_17:34:21.738.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Luiz Gustavode Almeida
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-03 16:22:00	ID requested
⏵ 1	2023-05-03 17:34:22	announced

Dataset with its publication pending

submitter keyword: Colonic epithelium

cathelicidin

goblet cells

mucus

Citrobacter rodentium

reactive oxygen species

AntoineDufour
contact affiliation	Department of Biochemistry and Molecular Biology, University of Calgary, Alberta, Canada; Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada; The Hotchkiss Brain Institute, University of Calgary, Alberta, Canada; McCaig Institute for Bone and Joint Health, University of Calgary, Alberta, Canada
contact email	antoine.dufour@ucalgary.ca
lab head
Luiz Gustavode Almeida
contact affiliation	University of Calgary
contact email	luizgustavo.biotec@hotmail.com
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/2023/05/PXD041957

PRIDE project URI

• PRIDE
  1. PXD041957
     1. Label: PRIDE project
     2. Name: Cathelicidin deficiency disrupts goblet cell mucus secretion but not mucus associated proteins in Citrobacter rodentium-induced colitis