PXD007542

PXD007542 is an original dataset announced via ProteomeXchange.

Title	The immune receptor TLR2 directly binds and signals immune activation to oligomeric chitin
Description	Chitin is the second most abundant polysaccharide in nature and a biomolecule intimately linked to fungal infection and allergic asthma, conditions that affect millions of patients worldwide. Chitin is known to stimulate multiple mammalian immune cells, but the precise molecular sensing mechanism has not been elucidated, hampering strategies to specifically target chitin-mediated pathologies. Using defined chitin oligomers we here identify six chitin subunits as the smallest immunologically active chitin motif and the innate immune receptor TLR2 as the molecular chitin sensor on human and murine immune cells, in vitro and in vivo. Chitin oligomers directly bound TLR2 with nanomolar affinity and elicited overlapping yet distinct signaling outcomes compared to canonical TLR2 ligands. Conversely, chitin oligomers composed of five chitin subunits acted as antagonists of chitin-TLR2 immune activation, hinting to an anti-inflammatory loop already known from plants, to also operate in humans. Of note, small chitin oligomers and biological-based blocking of the TLR2-chitin interaction effectively prevented chitin-mediated inflammation not only in vitro but also in vivo. Collectively, our study elucidates the molecular basis of how chitin is sensed by mammalian immune cells, which has broad impact for chitin-associated inflammatory pathologies. From a translational perspective, our findings further suggests that differently sized chitin oligomers could be developed into novel vaccine adjuvants or immuno-modulatory antagonists for the prevention or treatment of chitin-driven diseases in humans.
HostingRepository	PRIDE
AnnounceDate	2019-11-12
AnnouncementXML	Submission_2019-11-12_09:40:39.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nicolas Nalpas
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2017-08-24 02:34:39	ID requested
⏵ 1	2019-11-12 09:40:41	announced

El Maadidi S, Weber ANR, Motshwene P, Sch, ü, ssler JM, Backes D, Dickh, ö, fer S, Wang H, Liu X, Garcia MD, Taumer C, Soufi B, Wolz OO, Klimosch SN, Franz-Wachtel M, Macek B, Gay NJ, Putative link between Polo-like kinases (PLKs) and Toll-like receptor (TLR) signaling in transformed and primary human immune cells. Sci Rep, 9(1):13168(2019) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: LC-MSMS, Chitin, Pam2CSK4, THP-1, Macrophage, Phosphoproteomics, TLR

Alexander N.R. Weber
contact affiliation	Interfaculty Institute for Cell Biology Department of Immunology University of Tübingen Auf der Morgenstelle 15 72076 Tübingen Germany
contact email	alexander.weber@uni-tuebingen.de
lab head
Nicolas Nalpas
contact affiliation	Tuebingen University
contact email	nalpas.nicolas@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007542
     1. Label: PRIDE project
     2. Name: The immune receptor TLR2 directly binds and signals immune activation to oligomeric chitin