Toll-like receptor (TLR) 2 mediates inflammatory responses to oligomerized RrgA pneumococcal pilus type 1 protein
Golenbock, Douglas T.
UMass Chan AffiliationsDepartment of Medicine, Division of Infectious Diseases and Immunology
Document TypeJournal Article
Cell Surface Protein
Toll-like Receptors (TLR)
Biochemistry, Biophysics, and Structural Biology
Immunology and Infectious Disease
MetadataShow full item record
AbstractThe pneumococcal type 1 pilus is an inflammatory and adherence-promoting structure associated with increased virulence in mouse models. We show that RrgA, an ancillary pilus subunit devoid of a lipidation motif, particularly when presented as part of an oligomer, is a TLR2 agonist. The surface-exposed domain III, and in particular a 49-amino acid sequence (P3), of the protein is responsible for the TLR2 activity of RrgA. A pneumococcal mutant carrying RrgA with a deletion of the P3 region was significantly reduced in its ability to activate TLR2 and induce TNF-alpha responses after mouse intraperitoneal infection, whereas no such difference could be noted when TLR2(-/-) mice were challenged, further implicating this region in recognition by TLR2. Thus, we conclude that the type 1 pneumococcal pilus can activate cells via TLR2, and the ancillary pilus subunit RrgA is a key component of this activation.
J Biol Chem. 2013 Jan 25;288(4):2665-75. doi: 10.1074/jbc.M112.398875. Epub 2012 Dec 11. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/35155
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