PXD018752

PXD018752 is an original dataset announced via ProteomeXchange.

Title	Role of Mincle overexpression in pneumococcal pneumonia
Description	Macrophage-inducible C-type lectin (Mincle) dependent sensing of pathogens trig-gers proinflammatory immune responses in professional phagocytes that contribute to protect the host against pathogen invasion. Here, we examined whether overex-pression of Mincle designed to improve early pathogen sensing by professional phagocytes would improve lung protective immunity against Streptococcus pneu-moniae in mice. Proteomic profiling of alveolar macrophages (AM) of Mincle trans-genic (tg) mice stimulated with the Mincle-specific pneumococcal ligand glucosyl-diacylglycerol (Glc-DAG) revealed increased Nlrp3 inflammasome activation and downstream IL-1 cytokine release that was not observed in Glc-DAG stimulated Mincle KO or Nlrp3 KO macrophages. Along this line, Mincle tg mice also responded with a stronger Nlrp3 expression and early proinflammatory cytokine release after challenge with S. pneumoniae, ultimately leading to fatal pneumonia in the Mincle tg mice. Importantly, Nlrp3 inhibitor treatment of Mincle tg mice significantly mitigated the observed hyperinflammatory response to pneumococcal challenge. Together, we show that overexpression of the pattern recognition receptor Mincle triggers in-creased Glc-DAG dependent Nlrp3 inflammasome activation in professional phago-cytes leading to fatal pneumococcal pneumonia in mice, which is amenable to Nlrp3 inhibitor treatment. These data show that ectopic expression of Mincle receptor con-fers increased susceptibility rather than resistance to S. pneumoniae in mice, thus highlighting the importance of an inducible Mincle receptor expression in response to microbial challenge.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:13:09.273.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Picjh
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidoethyl-L-cysteine; monohydroxylated residue; acetylated residue; deamidated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-23 01:02:35	ID requested
1	2020-10-05 14:29:41	announced
2	2020-11-11 09:11:25	announced	2020-11-11: Updated publication reference for PubMed record(s): 33158955.
⏵ 3	2024-10-22 05:13:10	announced	2024-10-22: Updated project metadata.

Hollwedel FD, Maus R, Stolper J, Khan A, Stocker BL, Timmer MSM, Lu X, Pich A, Welte T, Yamasaki S, Maus UA, with Fatal Outcome in Mice. J Immunol, 205(12):3390-3399(2020) [pubmed]

10.4049/jimmunol.2000509;

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: innate immunity, lung,Mincle, S. pneumoniae, Nlrp3, Glc-DAG

Andreas Pich
contact affiliation	Hannover Medical School
contact email	pich.andreas@mh-hannover.de
lab head
Andreas Picjh
contact affiliation	Hannover Medical School Core Facility Proteomics
contact email	pich.andreas@mh-hannover.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018752
     1. Label: PRIDE project
     2. Name: Role of Mincle overexpression in pneumococcal pneumonia