T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice.
Streptococcus pneumoniae is an important human pathogen responsible for a spectrum of diseases including pneumonia. Immunological and pro-inflammatory processes induced in the lung during pneumococcal infection are well documented, but little is known about the role played by immunoregulatory cells...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002660&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850224661232615424 |
|---|---|
| author | Daniel R Neill Vitor E Fernandes Laura Wisby Andrew R Haynes Daniela M Ferreira Ameera Laher Natalie Strickland Stephen B Gordon Paul Denny Aras Kadioglu Peter W Andrew |
| author_facet | Daniel R Neill Vitor E Fernandes Laura Wisby Andrew R Haynes Daniela M Ferreira Ameera Laher Natalie Strickland Stephen B Gordon Paul Denny Aras Kadioglu Peter W Andrew |
| author_sort | Daniel R Neill |
| collection | DOAJ |
| description | Streptococcus pneumoniae is an important human pathogen responsible for a spectrum of diseases including pneumonia. Immunological and pro-inflammatory processes induced in the lung during pneumococcal infection are well documented, but little is known about the role played by immunoregulatory cells and cytokines in the control of such responses. We demonstrate considerable differences in the immunomodulatory cytokine transforming growth factor (TGF)-β between the pneumococcal pneumonia resistant BALB/c and susceptible CBA/Ca mouse strains. Immunohistochemistry and flow cytometry reveal higher levels of TGF-β protein in BALB/c lungs during pneumococcal pneumonia that correlates with a rapid rise in lung Foxp3(+)Helios(+) T regulatory cells. These cells have protective functions during pneumococcal pneumonia, because blocking their induction with an inhibitor of TGF-β impairs BALB/c resistance to infection and aids bacterial dissemination from lungs. Conversely, adoptive transfer of T regulatory cells to CBA/Ca mice, prior to infection, prolongs survival and decreases bacterial dissemination from lungs to blood. Importantly, strong T regulatory cell responses also correlate with disease-resistance in outbred MF1 mice, confirming the importance of immunoregulatory cells in controlling protective responses to the pneumococcus. This study provides exciting new evidence for the importance of immunomodulation during pulmonary pneumococcal infection and suggests that TGF-β signalling is a potential target for immunotherapy or drug design. |
| format | Article |
| id | doaj-art-55f2190d13d3436b97f37e54b2aa69fc |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-55f2190d13d3436b97f37e54b2aa69fc2025-08-20T02:05:34ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-01-0184e100266010.1371/journal.ppat.1002660T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice.Daniel R NeillVitor E FernandesLaura WisbyAndrew R HaynesDaniela M FerreiraAmeera LaherNatalie StricklandStephen B GordonPaul DennyAras KadiogluPeter W AndrewStreptococcus pneumoniae is an important human pathogen responsible for a spectrum of diseases including pneumonia. Immunological and pro-inflammatory processes induced in the lung during pneumococcal infection are well documented, but little is known about the role played by immunoregulatory cells and cytokines in the control of such responses. We demonstrate considerable differences in the immunomodulatory cytokine transforming growth factor (TGF)-β between the pneumococcal pneumonia resistant BALB/c and susceptible CBA/Ca mouse strains. Immunohistochemistry and flow cytometry reveal higher levels of TGF-β protein in BALB/c lungs during pneumococcal pneumonia that correlates with a rapid rise in lung Foxp3(+)Helios(+) T regulatory cells. These cells have protective functions during pneumococcal pneumonia, because blocking their induction with an inhibitor of TGF-β impairs BALB/c resistance to infection and aids bacterial dissemination from lungs. Conversely, adoptive transfer of T regulatory cells to CBA/Ca mice, prior to infection, prolongs survival and decreases bacterial dissemination from lungs to blood. Importantly, strong T regulatory cell responses also correlate with disease-resistance in outbred MF1 mice, confirming the importance of immunoregulatory cells in controlling protective responses to the pneumococcus. This study provides exciting new evidence for the importance of immunomodulation during pulmonary pneumococcal infection and suggests that TGF-β signalling is a potential target for immunotherapy or drug design.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002660&type=printable |
| spellingShingle | Daniel R Neill Vitor E Fernandes Laura Wisby Andrew R Haynes Daniela M Ferreira Ameera Laher Natalie Strickland Stephen B Gordon Paul Denny Aras Kadioglu Peter W Andrew T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice. PLoS Pathogens |
| title | T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice. |
| title_full | T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice. |
| title_fullStr | T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice. |
| title_full_unstemmed | T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice. |
| title_short | T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice. |
| title_sort | t regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002660&type=printable |
| work_keys_str_mv | AT danielrneill tregulatorycellscontrolsusceptibilitytoinvasivepneumococcalpneumoniainmice AT vitorefernandes tregulatorycellscontrolsusceptibilitytoinvasivepneumococcalpneumoniainmice AT laurawisby tregulatorycellscontrolsusceptibilitytoinvasivepneumococcalpneumoniainmice AT andrewrhaynes tregulatorycellscontrolsusceptibilitytoinvasivepneumococcalpneumoniainmice AT danielamferreira tregulatorycellscontrolsusceptibilitytoinvasivepneumococcalpneumoniainmice AT ameeralaher tregulatorycellscontrolsusceptibilitytoinvasivepneumococcalpneumoniainmice AT nataliestrickland tregulatorycellscontrolsusceptibilitytoinvasivepneumococcalpneumoniainmice AT stephenbgordon tregulatorycellscontrolsusceptibilitytoinvasivepneumococcalpneumoniainmice AT pauldenny tregulatorycellscontrolsusceptibilitytoinvasivepneumococcalpneumoniainmice AT araskadioglu tregulatorycellscontrolsusceptibilitytoinvasivepneumococcalpneumoniainmice AT peterwandrew tregulatorycellscontrolsusceptibilitytoinvasivepneumococcalpneumoniainmice |