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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/55f2190d13d3436b97f37e54b2aa69fc
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spelling	oai:doaj.org-article:55f2190d13d3436b97f37e54b2aa69fc2021-11-18T06:04:30ZT regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice.1553-73661553-737410.1371/journal.ppat.1002660https://doaj.org/article/55f2190d13d3436b97f37e54b2aa69fc2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22563306/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Streptococcus 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.Daniel R NeillVitor E FernandesLaura WisbyAndrew R HaynesDaniela M FerreiraAmeera LaherNatalie StricklandStephen B GordonPaul DennyAras KadiogluPeter W AndrewPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 4, p e1002660 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 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.
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
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
title	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_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_sort	t regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/55f2190d13d3436b97f37e54b2aa69fc
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T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice.

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