Mast Cells Are Activated by Streptococcus pneumoniae In Vitro but Dispensable for the Host Defense Against Pneumococcal Central Nervous System Infection In Vivo
Mast cells reside on and near the cerebral vasculature, the predominant site of pneumococcal entry into the central nervous system (CNS). Although mast cells have been reported to be crucial in protecting from systemic bacterial infections, their role in bacterial infections of the CNS remained elus...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-03-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00550/full |
| _version_ | 1828483279586590720 |
|---|---|
| author | Johanna Fritscher Daniel Amberger Susanne Dyckhoff Jan Philipp Bewersdorf Ilias Masouris Stefanie Voelk Sven Hammerschmidt Helga Maria Schmetzer Matthias Klein Hans-Walter Pfister Uwe Koedel |
| author_facet | Johanna Fritscher Daniel Amberger Susanne Dyckhoff Jan Philipp Bewersdorf Ilias Masouris Stefanie Voelk Sven Hammerschmidt Helga Maria Schmetzer Matthias Klein Hans-Walter Pfister Uwe Koedel |
| author_sort | Johanna Fritscher |
| collection | DOAJ |
| description | Mast cells reside on and near the cerebral vasculature, the predominant site of pneumococcal entry into the central nervous system (CNS). Although mast cells have been reported to be crucial in protecting from systemic bacterial infections, their role in bacterial infections of the CNS remained elusive. Here, we assessed the role of mast cells in pneumococcal infection in vitro and in vivo. In introductory experiments using mouse bone marrow-derived mast cells (BMMC), we found that (i) BMMC degranulate and release selected cytokines upon exposure to Streptococcus pneumoniae, (ii) the response of BMMC varies between different pneumococcal serotypes and (iii) is dependent on pneumolysin. Intriguingly though, apart from a slight enhancement of cerebrospinal fluid (CSF) pleocytosis, neither two different mast cell-deficient Kit mutant mouse strains (WBB6F1-KitW/Wv and C57BL/6 KitW-sh/W-sh mice) nor pharmacologic mast cell stabilization with cromoglycate had any significant impact on the disease phenotype of experimental pneumococcal meningitis. The incomplete reversal of the enhanced CSF pleocytosis by local mast cell engraftment suggests that this phenomenon is caused by other c-Kit mutation-related mechanisms than mast cell deficiency. In conclusion, our study suggests that mast cells can be activated by S. pneumoniae in vitro. However, mast cells do not play a significant role as sentinels of pneumococcal CSF invasion and initiators of innate immunity in vivo. |
| first_indexed | 2024-12-11T08:33:24Z |
| format | Article |
| id | doaj.art-450e8bc3b5b14976b44bda79681b8eb8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T08:33:24Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-450e8bc3b5b14976b44bda79681b8eb82022-12-22T01:14:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-03-01910.3389/fimmu.2018.00550323552Mast Cells Are Activated by Streptococcus pneumoniae In Vitro but Dispensable for the Host Defense Against Pneumococcal Central Nervous System Infection In VivoJohanna Fritscher0Daniel Amberger1Susanne Dyckhoff2Jan Philipp Bewersdorf3Ilias Masouris4Stefanie Voelk5Sven Hammerschmidt6Helga Maria Schmetzer7Matthias Klein8Hans-Walter Pfister9Uwe Koedel10Department of Neurology, University Hospital, Ludwig-Maximilians-University, Munich, GermanyDepartment of Internal Medicine III (Oncology), University Hospital, Ludwig-Maximilians-University, Munich, GermanyDepartment of Neurology, University Hospital, Ludwig-Maximilians-University, Munich, GermanyDepartment of Neurology, University Hospital, Ludwig-Maximilians-University, Munich, GermanyDepartment of Neurology, University Hospital, Ludwig-Maximilians-University, Munich, GermanyDepartment of Neurology, University Hospital, Ludwig-Maximilians-University, Munich, GermanyDepartment of Molecular Genetics and Infection Biology, Interfaculty Institute for Genetics and Functional Genomics, Center for Functional Genomics of Microbes, Ernst Moritz Arndt University Greifswald, Greifswald, GermanyDepartment of Internal Medicine III (Oncology), University Hospital, Ludwig-Maximilians-University, Munich, GermanyDepartment of Neurology, University Hospital, Ludwig-Maximilians-University, Munich, GermanyDepartment of Neurology, University Hospital, Ludwig-Maximilians-University, Munich, GermanyDepartment of Neurology, University Hospital, Ludwig-Maximilians-University, Munich, GermanyMast cells reside on and near the cerebral vasculature, the predominant site of pneumococcal entry into the central nervous system (CNS). Although mast cells have been reported to be crucial in protecting from systemic bacterial infections, their role in bacterial infections of the CNS remained elusive. Here, we assessed the role of mast cells in pneumococcal infection in vitro and in vivo. In introductory experiments using mouse bone marrow-derived mast cells (BMMC), we found that (i) BMMC degranulate and release selected cytokines upon exposure to Streptococcus pneumoniae, (ii) the response of BMMC varies between different pneumococcal serotypes and (iii) is dependent on pneumolysin. Intriguingly though, apart from a slight enhancement of cerebrospinal fluid (CSF) pleocytosis, neither two different mast cell-deficient Kit mutant mouse strains (WBB6F1-KitW/Wv and C57BL/6 KitW-sh/W-sh mice) nor pharmacologic mast cell stabilization with cromoglycate had any significant impact on the disease phenotype of experimental pneumococcal meningitis. The incomplete reversal of the enhanced CSF pleocytosis by local mast cell engraftment suggests that this phenomenon is caused by other c-Kit mutation-related mechanisms than mast cell deficiency. In conclusion, our study suggests that mast cells can be activated by S. pneumoniae in vitro. However, mast cells do not play a significant role as sentinels of pneumococcal CSF invasion and initiators of innate immunity in vivo.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00550/fullmast cellbacterial meningitisinnate immunityStreptococcus pneumoniaemouse model |
| spellingShingle | Johanna Fritscher Daniel Amberger Susanne Dyckhoff Jan Philipp Bewersdorf Ilias Masouris Stefanie Voelk Sven Hammerschmidt Helga Maria Schmetzer Matthias Klein Hans-Walter Pfister Uwe Koedel Mast Cells Are Activated by Streptococcus pneumoniae In Vitro but Dispensable for the Host Defense Against Pneumococcal Central Nervous System Infection In Vivo Frontiers in Immunology mast cell bacterial meningitis innate immunity Streptococcus pneumoniae mouse model |
| title | Mast Cells Are Activated by Streptococcus pneumoniae In Vitro but Dispensable for the Host Defense Against Pneumococcal Central Nervous System Infection In Vivo |
| title_full | Mast Cells Are Activated by Streptococcus pneumoniae In Vitro but Dispensable for the Host Defense Against Pneumococcal Central Nervous System Infection In Vivo |
| title_fullStr | Mast Cells Are Activated by Streptococcus pneumoniae In Vitro but Dispensable for the Host Defense Against Pneumococcal Central Nervous System Infection In Vivo |
| title_full_unstemmed | Mast Cells Are Activated by Streptococcus pneumoniae In Vitro but Dispensable for the Host Defense Against Pneumococcal Central Nervous System Infection In Vivo |
| title_short | Mast Cells Are Activated by Streptococcus pneumoniae In Vitro but Dispensable for the Host Defense Against Pneumococcal Central Nervous System Infection In Vivo |
| title_sort | mast cells are activated by streptococcus pneumoniae in vitro but dispensable for the host defense against pneumococcal central nervous system infection in vivo |
| topic | mast cell bacterial meningitis innate immunity Streptococcus pneumoniae mouse model |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00550/full |
| work_keys_str_mv | AT johannafritscher mastcellsareactivatedbystreptococcuspneumoniaeinvitrobutdispensableforthehostdefenseagainstpneumococcalcentralnervoussysteminfectioninvivo AT danielamberger mastcellsareactivatedbystreptococcuspneumoniaeinvitrobutdispensableforthehostdefenseagainstpneumococcalcentralnervoussysteminfectioninvivo AT susannedyckhoff mastcellsareactivatedbystreptococcuspneumoniaeinvitrobutdispensableforthehostdefenseagainstpneumococcalcentralnervoussysteminfectioninvivo AT janphilippbewersdorf mastcellsareactivatedbystreptococcuspneumoniaeinvitrobutdispensableforthehostdefenseagainstpneumococcalcentralnervoussysteminfectioninvivo AT iliasmasouris mastcellsareactivatedbystreptococcuspneumoniaeinvitrobutdispensableforthehostdefenseagainstpneumococcalcentralnervoussysteminfectioninvivo AT stefanievoelk mastcellsareactivatedbystreptococcuspneumoniaeinvitrobutdispensableforthehostdefenseagainstpneumococcalcentralnervoussysteminfectioninvivo AT svenhammerschmidt mastcellsareactivatedbystreptococcuspneumoniaeinvitrobutdispensableforthehostdefenseagainstpneumococcalcentralnervoussysteminfectioninvivo AT helgamariaschmetzer mastcellsareactivatedbystreptococcuspneumoniaeinvitrobutdispensableforthehostdefenseagainstpneumococcalcentralnervoussysteminfectioninvivo AT matthiasklein mastcellsareactivatedbystreptococcuspneumoniaeinvitrobutdispensableforthehostdefenseagainstpneumococcalcentralnervoussysteminfectioninvivo AT hanswalterpfister mastcellsareactivatedbystreptococcuspneumoniaeinvitrobutdispensableforthehostdefenseagainstpneumococcalcentralnervoussysteminfectioninvivo AT uwekoedel mastcellsareactivatedbystreptococcuspneumoniaeinvitrobutdispensableforthehostdefenseagainstpneumococcalcentralnervoussysteminfectioninvivo |