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

PLoS Pathogens
Daniel R NeillPeter W Andrew

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 ...Continue Reading

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Citations

Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Youssif Mohammed AliWilhelm J Schwaeble
Apr 23, 2014·American Journal of Respiratory and Critical Care Medicine·Daniel R NeillAras Kadioglu
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Methods Mentioned

BETA
flow cytometry
Reverse
PCR
light microscopy

Software Mentioned

Helios
BioConductor R
CellQuest
Limma
FlowJo
Genepix pro
IPA
Graph Pad Prism

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