title: Toll-like receptor (TLR) 2 mediates inflammatory responses to oligomerized RrgA pneumococcal pilus type 1 protein.
abstract: The 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-α 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.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Basset
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Cyril
authors.initials: C
authors.lastname: Benes
authors.forename: Sabina
authors.initials: S
authors.lastname: Sayeed
authors.forename: Muriel
authors.initials: M
authors.lastname: Herd
authors.forename: Claudette
authors.initials: C
authors.lastname: Thompson
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Golenbock
authors.forename: Andrew
authors.initials: A
authors.lastname: Camilli
authors.forename: Richard
authors.initials: R
authors.lastname: Malley
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D036781:Fimbriae Proteins / Q000235:genetics / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D017353:Gene Deletion; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D017434:Protein Structure, Tertiary; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000378:metabolism*; D013499:Surface Properties; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C579340:RrgA protein, Streptococcus pneumoniae; D051195:Toll-Like Receptor 2; D037521:Virulence Factors; D036781:Fimbriae Proteins