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T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice.

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journal contribution
posted on 24.06.2013, 13:04 by 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
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.

History

Citation

PLoS Pathogens, 2012, 8 (4), e1002660.

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

PLoS Pathogens

Publisher

Public Library of Science

issn

1553-7366

eissn

1553-7374

Copyright date

2012

Available date

24/06/2013

Publisher version

http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002660

Language

en