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Toll-Like Receptor Signalling Is Not Involved in Platelet Response to Streptococcus pneumoniae In Vitro or In Vivo
Streptococcus (S.) pneumoniae strains vary considerably in their ability to cause invasive disease in humans, which is at least in part determined by the capsular serotype. Platelets have been implicated as sentinel cells in the circulation for host defence. One of their utensils for this function i...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890788/ https://www.ncbi.nlm.nih.gov/pubmed/27253707 http://dx.doi.org/10.1371/journal.pone.0156977 |
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author | de Stoppelaar, Sacha F. Claushuis, Theodora A. M. Schaap, Marianne C. L. Hou, Baidong van der Poll, Tom Nieuwland, Rienk van ‘t Veer, Cornelis |
author_facet | de Stoppelaar, Sacha F. Claushuis, Theodora A. M. Schaap, Marianne C. L. Hou, Baidong van der Poll, Tom Nieuwland, Rienk van ‘t Veer, Cornelis |
author_sort | de Stoppelaar, Sacha F. |
collection | PubMed |
description | Streptococcus (S.) pneumoniae strains vary considerably in their ability to cause invasive disease in humans, which is at least in part determined by the capsular serotype. Platelets have been implicated as sentinel cells in the circulation for host defence. One of their utensils for this function is the expression of Toll-like receptors (TLRs). We here aimed to investigate platelet response to S. pneumoniae and a role for TLRs herein. Platelets were stimulated using four serotypes of S. pneumonia including an unencapsulated mutant strain. In vitro aggregation and flow cytometry assays were performed using blood of healthy volunteers, or blood of TLR knock out and WT mice. For in vivo pneumonia experiments, platelet specific Myd88 knockout (Plt-Myd88(-/-)) mice were used. We found that platelet aggregation was induced by unencapsulated S. pneumoniae only. Whole blood incubation with all S. pneumoniae serotypes tested resulted in platelet degranulation and platelet-leukocyte complex formation. Platelet activation was TLR independent, as responses were not inhibited by TLR blocking antibodies, not induced by TLR agonists and were equally induced in wild-type and Tlr2(-/-), Tlr4(-/-), Tlr2/4(-/-), Tlr9(-/-) and Myd88(-/-) blood. Plt-Myd88(-/-) and control mice displayed no differences in bacterial clearance or immune response to pneumonia by unencapsulated S. pneumoniae. In conclusion, S. pneumoniae activates platelets through a TLR-independent mechanism that is impeded by the bacterial capsule. Additionally, platelet MyD88-dependent TLR signalling is not involved in host defence to unencapsulated S. pneumoniae in vivo. |
format | Online Article Text |
id | pubmed-4890788 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-48907882016-06-10 Toll-Like Receptor Signalling Is Not Involved in Platelet Response to Streptococcus pneumoniae In Vitro or In Vivo de Stoppelaar, Sacha F. Claushuis, Theodora A. M. Schaap, Marianne C. L. Hou, Baidong van der Poll, Tom Nieuwland, Rienk van ‘t Veer, Cornelis PLoS One Research Article Streptococcus (S.) pneumoniae strains vary considerably in their ability to cause invasive disease in humans, which is at least in part determined by the capsular serotype. Platelets have been implicated as sentinel cells in the circulation for host defence. One of their utensils for this function is the expression of Toll-like receptors (TLRs). We here aimed to investigate platelet response to S. pneumoniae and a role for TLRs herein. Platelets were stimulated using four serotypes of S. pneumonia including an unencapsulated mutant strain. In vitro aggregation and flow cytometry assays were performed using blood of healthy volunteers, or blood of TLR knock out and WT mice. For in vivo pneumonia experiments, platelet specific Myd88 knockout (Plt-Myd88(-/-)) mice were used. We found that platelet aggregation was induced by unencapsulated S. pneumoniae only. Whole blood incubation with all S. pneumoniae serotypes tested resulted in platelet degranulation and platelet-leukocyte complex formation. Platelet activation was TLR independent, as responses were not inhibited by TLR blocking antibodies, not induced by TLR agonists and were equally induced in wild-type and Tlr2(-/-), Tlr4(-/-), Tlr2/4(-/-), Tlr9(-/-) and Myd88(-/-) blood. Plt-Myd88(-/-) and control mice displayed no differences in bacterial clearance or immune response to pneumonia by unencapsulated S. pneumoniae. In conclusion, S. pneumoniae activates platelets through a TLR-independent mechanism that is impeded by the bacterial capsule. Additionally, platelet MyD88-dependent TLR signalling is not involved in host defence to unencapsulated S. pneumoniae in vivo. Public Library of Science 2016-06-02 /pmc/articles/PMC4890788/ /pubmed/27253707 http://dx.doi.org/10.1371/journal.pone.0156977 Text en © 2016 de Stoppelaar et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article de Stoppelaar, Sacha F. Claushuis, Theodora A. M. Schaap, Marianne C. L. Hou, Baidong van der Poll, Tom Nieuwland, Rienk van ‘t Veer, Cornelis Toll-Like Receptor Signalling Is Not Involved in Platelet Response to Streptococcus pneumoniae In Vitro or In Vivo |
title | Toll-Like Receptor Signalling Is Not Involved in Platelet Response to Streptococcus pneumoniae In Vitro or In Vivo |
title_full | Toll-Like Receptor Signalling Is Not Involved in Platelet Response to Streptococcus pneumoniae In Vitro or In Vivo |
title_fullStr | Toll-Like Receptor Signalling Is Not Involved in Platelet Response to Streptococcus pneumoniae In Vitro or In Vivo |
title_full_unstemmed | Toll-Like Receptor Signalling Is Not Involved in Platelet Response to Streptococcus pneumoniae In Vitro or In Vivo |
title_short | Toll-Like Receptor Signalling Is Not Involved in Platelet Response to Streptococcus pneumoniae In Vitro or In Vivo |
title_sort | toll-like receptor signalling is not involved in platelet response to streptococcus pneumoniae in vitro or in vivo |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890788/ https://www.ncbi.nlm.nih.gov/pubmed/27253707 http://dx.doi.org/10.1371/journal.pone.0156977 |
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