PXD012176

PXD012176 is an original dataset announced via ProteomeXchange.

Title	S. aureus drives expansion of low density neutrophils in the diabetic host
Description	Abstract S. aureus is a major opportunistic pathogen infecting patients with diabetes. Increased mortality was observed following IV S. aureus infection in diabetic mice compared to non-diabetic controls, correlating with increased numbers of low density neutrophils (LDNs) and neutrophil extracellular traps (NETs). LDN development is dependent on TGF?, which was more activated in the diabetic host. Neutralization of TGF?, or the integrin responsible for its activation ?5?8, reduced numbers of LDNs and improved survival. Comparison of high and low density neutrophils identified PTEN signaling as a central regulator of LDN NET release. Inhibition of PTEN improved survival and decreased NET production in infected diabetic mice. MEDI4893*, a monoclonal antibody that neutralizes alpha toxin (AT) in development for prevention of S. aureus infection, was able to block TGF? activation, reduce LDNs and NETs, and significantly improve survival. Our data identify a population of neutrophils in infected diabetic mice which correlated with decreased survival and increased NET production. Targeting a single virulence factor of S. aureus prevented emergence of the LDN population and improved survival, supporting potential use of pathogen specific antibodies for treating diabetic infections.
HostingRepository	PRIDE
AnnounceDate	2019-04-26
AnnouncementXML	Submission_2019-05-02_02:02:57.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Raghothama Chaerkady
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-24 02:12:37	ID requested
1	2019-04-26 10:27:49	announced
⏵ 2	2019-05-02 02:02:58	announced	Updated publication reference for PubMed record(s): 30985291.

Cohen TS, Takahashi V, Bonnell J, Tovchigrechko A, Chaerkady R, Yu W, Jones-Nelson O, Lee Y, Raja R, Hess S, Stover CK, Worthington JJ, Travis MA, Sellman BR, Staphylococcus aureus drives expansion of low-density neutrophils in diabetic mice. J Clin Invest, 129(5):2133-2144(2019) [pubmed]

submitter keyword: Tandem mass tags, HCD, MS2, MS3, neutrophils, S.aureus

Sonja Hess
contact affiliation	Medimmune LLC
contact email	hessso@medimmune.com
lab head
Raghothama Chaerkady
contact affiliation	MedImmune
contact email	chaerkadyr@medimmune.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/2019/04/PXD012176

PRIDE project URI

• PRIDE
  1. PXD012176
     1. Label: PRIDE project
     2. Name: S. aureus drives expansion of low density neutrophils in the diabetic host