Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/28005
Title: T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice.
Authors: Neill, Daniel R.
Fernandes, Vitor E.
Wisby, Laura
Haynes, Andrew R.
Ferreira, Daniela M.
Laher, Ameera
Strickland, Natalie
Gordon, Stephen B.
Denny, Paul
Kadioglu, Aras
Andrew, Peter W.
First Published: 19-Apr-2012
Publisher: Public Library of Science
Citation: PLoS Pathogens, 2012, 8 (4), e1002660.
Abstract: 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.
DOI Link: 10.1371/journal.ppat.1002660
ISSN: 1553-7366
eISSN: 1553-7374
Links: http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002660
http://hdl.handle.net/2381/28005
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright: © 2012 Neill et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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