title: Heterogeneity of host TLR2 stimulation by Staphylocoocus aureus isolates.
abstract: High lipoprotein expression and potent activation of host Toll-like receptor-2 (TLR2) are characteristic features of the staphylococcal species. Expression of TLR2 in the host is important for clearance of Staphylococcus aureus infection and host survival. Thus, we hypothesized that bacterial regulation of its intrinsic TLR2-stimulatory capacity could represent a means for immune evasion or host adaptation. We, therefore, compared clinical S. aureus isolates in regards to their TLR2 activation potential and assessed the bacterial factors that modulate TLR2-mediated recognition. S. aureus isolates displayed considerable variability in TLR2-activity with low to absent TLR2-activity in 64% of the isolates tested (68/106). Notably, strain-specific TLR2-activity was independent of the strain origin, e.g. no differences were found between strains isolated from respiratory specimen from cystic fibrosis patients or those isolated from invasive disease specimen. TLR2-activity correlated with protein A expression but not with the agr status. Capsule expression and small colony variant formation had a negative impact on TLR2-activity but any disruption of cell wall integrity enhanced TLR2 activation. Altogether, heterogeneity in host TLR2-activity reflects differences in metabolic activity and cell wall synthesis and/or remodeling.
authors.affiliation: Department for Infectious Disease, Medical Microbiology and Hygiene, University Hospital Heidelberg, Heidelberg, Germany; Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Dina
authors.initials: D
authors.lastname: Hilmi
authors.affiliation: Department for Infectious Disease, Medical Microbiology and Hygiene, University Hospital Heidelberg, Heidelberg, Germany; Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Marijo
authors.initials: M
authors.lastname: Parcina
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stollewerk
authors.affiliation: Department for Infectious Disease, Medical Microbiology and Hygiene, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Ostrop
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Michaele
authors.initials: M
authors.lastname: Josten
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Alina
authors.initials: A
authors.lastname: Meilaender
authors.affiliation: LG Immunchemie, Research Center Borstel, Borstel, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zaehringer
authors.affiliation: Institute of Medical Microbiology and Infection Control, Hospital of Goethe-University, Frankfurt am Main, Germany.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Wichelhaus
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Bierbaum
authors.affiliation: Department for Infectious Disease, Medical Microbiology and Hygiene, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Heeg
authors.affiliation: IMIT-Interfakultäres Institut für Mikrobiologie und Infektionsmedizin, Universitätsklinikum Tuebingen, Tuebingen, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Wolz
authors.affiliation: Department for Infectious Disease, Medical Microbiology and Hygiene, University Hospital Heidelberg, Heidelberg, Germany; Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bekeredjian-Ding
mesh_terms: D002473:Cell Wall / Q000276:immunology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate; D008074:Lipoproteins / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000302:isolation & purification / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
chemical_list: D008074:Lipoproteins; D051195:Toll-Like Receptor 2