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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., ((c) 2009 Elsevier B.V. All rights reserved.)

Interaction of Streptococcus suis with primary porcine alveolar macrophages was studied using transcriptomics. Transcriptional response of macrophages to two different S. suis strains was studied: wild-type S10 that is resistant to phagocytosis, and its non-encapsulated mutant that is phagocytosed efficiently. The macrophages' transcriptional response was observed only after 60 min of incubation. Eleven genes were expressed significantly different between macrophages infected with streptococci and control mock-infected macrophages. These genes include IL-1-beta, MIP-2-alpha and TNF-alpha. When gene expression was studied as a function of time, transcriptional changes occurred in all macrophages independent of streptococci. The fold induction of induced genes however, was much stronger in macrophages incubated with the non-encapsulated S. suis strain that was phagocytosed. The genes that were higher induced due to S. suis suggest an innate immune response is induced in macrophages. Pathway analysis revealed that genes that are part of the putative MAP-kinase signal transduction system are over-represented among the regulated genes. Using an immortalized alveolar macrophage cell line it was shown that macrophages respond to interaction with S. suis by the translocation of NF-kappaB to the nucleus, independent of phagocytosis. This translocation subsequently induced expression of innate immune genes. This strongly suggests besides the MAP-kinase signaling pathway, NF-kappaB signaling is also induced upon interaction with S. suis., (Copyright 2009 Elsevier B.V. All rights reserved.)