title: Differential activation of the Toll-like receptor 2/6 complex by lipoproteins of Streptococcus suis serotypes 2 and 9.
abstract: Streptococcus suis causes invasive infections in pigs and occasionally in humans. Worldwide, S. suis serotype 2 is most frequently isolated from diseased piglets, but the less virulent serotype 9 is emerging, at least in Europe. We compared the activation of human Toll-like receptors (hTLRs) by S. suis serotype 2 and 9 strains to better understand the role of the innate immune response in fighting S. suis infections. Neither live nor heat-killed log phase grown S. suis activated the hTLR1/2, hTLR2/6 and hTLR4/MD-2 complexes. However, the hTLR2/6 complex was specifically activated by both serotypes after disruption of the cell wall synthesis using penicillin. Activation levels of the hTLR2/6 complex were higher for serotype 9 strains compared to serotype 2 strains suggesting intrinsic differences in cell wall composition between both serotypes. The hTLR2/6 activating fractions decreased in molecular size after digestion with proteinase K and were sensitive for lipoprotein lipase digestion and NaOH hydrolysis, indicating lipoprotein(s) as active component(s). Overall, our results indicate that S. suis lipoproteins activate TLR2/6 but not TLR1/2 and that the clinically different serotypes 2 and 9 display differential release of TLR ligand when cell wall integrity is compromised.
authors.affiliation: Central Veterinary Institute, Wageningen UR, Edelhertweg 15, 8219 PH Lelystad, The Netherlands. paul.wichgersschreur@wur.nl
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Wichgers Schreur
authors.forename: Johanna M J
authors.initials: JM
authors.lastname: Rebel
authors.forename: Mari A
authors.initials: MA
authors.lastname: Smits
authors.forename: Jos P M
authors.initials: JP
authors.lastname: van Putten
authors.forename: Hilde E
authors.initials: HE
authors.lastname: Smith
mesh_terms: D036022:Capsid Proteins; D002473:Cell Wall; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008074:Lipoproteins / Q000494:pharmacology*; D010406:Penicillins; D017011:Streptococcus suis / Q000145:classification* / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; D008074:Lipoproteins; D010406:Penicillins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C018315:hexon capsid protein, Adenovirus