Toll-like receptor-dependent discrimination of streptococci.
Streptococcus pneumoniae and Streptococcus agalactiae cause distinct infectious diseases in small children. Similarly, these bacteria elicit very different host-cell responses in vitro. Inactivated S. agalactiae by far exceeds S. pneumoniae in the activation of inflammatory cytokines and upstream signaling intermediates such as the MAP kinase JNK. The inflammatory response to both Streptococcus spp. is mediated by MyD88, an essential adapter protein of Toll-like receptors (TLRs), although the specific TLRs that are involved have not been fully resolved. Furthermore, during logarithmic growth, S. pneumoniae releases pneumolysin that interacts with TLR4 whereas S. agalactiae releases diacylated molecules that interact with TLR2/6. Interaction of these soluble bacterial products with their cognate TLRs is critical for limiting bacterial dissemination and and systemic inflammation in mice. This might be due, in part, to TLR-mediated apoptosis induced by these factors. In conclusion related streptococcal species induce specific events in TLR-mediated signal transduction. Comparative analysis of the host-cell response to these bacteria reveals molecules such as JNK as valuable targets for adjunctive sepsis therapy.
Santos-Sierra
Sandra
S
Division of Infectious Diseases, Children's Hospital, Freiburg University, Freiburg, Germany.
Golenbock
Douglas T
DT
Henneke
Philipp
P
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000276:immunology / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007231:Infant, Newborn; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013292:Streptococcus agalactiae / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D013301:Streptolysins / Q000378:metabolism; D013682:Teichoic Acids / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism*
D001426:Bacterial Proteins; D008024:Ligands; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D013301:Streptolysins; D013682:Teichoic Acids; D051193:Toll-Like Receptors; C032290:plY protein, Streptococcus pneumoniae; C009900:lipoteichoic acid; D048031:JNK Mitogen-Activated Protein Kinases