2.50
HDL Handle:
http://hdl.handle.net/10033/48314
Title:
Immune recognition of Streptococcus pyogenes by dendritic cells.
Authors:
Loof, Torsten G; Goldmann, Oliver; Medina, Eva
Abstract:
Streptococcus pyogenes is one of the most frequent human pathogens. Recent studies have identified dendritic cells (DCs) as important contributors to host defense against S. pyogenes. The objective of this study was to identify the receptors involved in immune recognition of S. pyogenes by DCs. To determine whether Toll-like receptors (TLRs) were involved in DC sensing of S. pyogenes, we evaluated the response of bone marrow-derived DCs obtained from mice deficient in MyD88, an adapter molecule used by almost all TLRs, following S. pyogenes stimulation. Despite the fact that MyD88(-/-) DCs did not differ from wild-type DCs in the ability to internalize and kill S. pyogenes, the up-regulation of maturation markers, such as CD40, CD80, and CD86, and the production of inflammatory cytokines, such as interleukin-12 (IL-12), IL-6, and tumor necrosis factor alpha, were dramatically impaired in S. pyogenes-stimulated MyD88(-/-) DCs. These results suggest that signaling through TLRs is the principal pathway by which DCs sense S. pyogenes and become activated. Surprisingly, DCs deficient in signaling through each of the TLRs reported as potential receptors for gram-positive cell components, such as TLR1, TLR2, TLR4, TLR9, and TLR2/6, were not impaired in the secretion of proinflammatory cytokines and the up-regulation of costimulatory molecules after S. pyogenes stimulation. In conclusion, our results exclude a major involvement of a single TLR or the heterodimer TLR2/6 in S. pyogenes sensing by DCs and argue for a multimodal recognition in which a combination of several different TLR-mediated signals is essential for a rapid and effective response to the pathogen.
Affiliation:
Infection Immunology Research Group, Department of Microbial Pathogenesis, Helmholtz Center for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Citation:
Immune recognition of Streptococcus pyogenes by dendritic cells. 2008, 76 (6):2785-92 Infect. Immun.
Journal:
Infection and immunity
Issue Date:
Jun-2008
URI:
http://hdl.handle.net/10033/48314
DOI:
10.1128/IAI.01680-07
PubMed ID:
18391010
Type:
Article
Language:
en
ISSN:
1098-5522
Appears in Collections:
Publications of RG Infection Immunology (INI)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorLoof, Torsten G-
dc.contributor.authorGoldmann, Oliver-
dc.contributor.authorMedina, Eva-
dc.date.accessioned2009-02-02T08:57:16Z-
dc.date.available2009-02-02T08:57:16Z-
dc.date.issued2008-06-
dc.identifier.citationImmune recognition of Streptococcus pyogenes by dendritic cells. 2008, 76 (6):2785-92 Infect. Immun.en
dc.identifier.issn1098-5522-
dc.identifier.pmid18391010-
dc.identifier.doi10.1128/IAI.01680-07-
dc.identifier.urihttp://hdl.handle.net/10033/48314-
dc.description.abstractStreptococcus pyogenes is one of the most frequent human pathogens. Recent studies have identified dendritic cells (DCs) as important contributors to host defense against S. pyogenes. The objective of this study was to identify the receptors involved in immune recognition of S. pyogenes by DCs. To determine whether Toll-like receptors (TLRs) were involved in DC sensing of S. pyogenes, we evaluated the response of bone marrow-derived DCs obtained from mice deficient in MyD88, an adapter molecule used by almost all TLRs, following S. pyogenes stimulation. Despite the fact that MyD88(-/-) DCs did not differ from wild-type DCs in the ability to internalize and kill S. pyogenes, the up-regulation of maturation markers, such as CD40, CD80, and CD86, and the production of inflammatory cytokines, such as interleukin-12 (IL-12), IL-6, and tumor necrosis factor alpha, were dramatically impaired in S. pyogenes-stimulated MyD88(-/-) DCs. These results suggest that signaling through TLRs is the principal pathway by which DCs sense S. pyogenes and become activated. Surprisingly, DCs deficient in signaling through each of the TLRs reported as potential receptors for gram-positive cell components, such as TLR1, TLR2, TLR4, TLR9, and TLR2/6, were not impaired in the secretion of proinflammatory cytokines and the up-regulation of costimulatory molecules after S. pyogenes stimulation. In conclusion, our results exclude a major involvement of a single TLR or the heterodimer TLR2/6 in S. pyogenes sensing by DCs and argue for a multimodal recognition in which a combination of several different TLR-mediated signals is essential for a rapid and effective response to the pathogen.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshCells, Cultureden
dc.subject.meshCytokinesen
dc.subject.meshDendritic Cellsen
dc.subject.meshGene Expression Regulationen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Knockouten
dc.subject.meshMyeloid Differentiation Factor 88en
dc.subject.meshPhagocytosisen
dc.subject.meshSpecific Pathogen-Free Organismsen
dc.subject.meshStreptococcus pyogenesen
dc.subject.meshToll-Like Receptor 2en
dc.subject.meshToll-Like Receptor 9en
dc.titleImmune recognition of Streptococcus pyogenes by dendritic cells.en
dc.typeArticleen
dc.contributor.departmentInfection Immunology Research Group, Department of Microbial Pathogenesis, Helmholtz Center for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany.en
dc.identifier.journalInfection and immunityen

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