Imperial College London
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DrThomasClarke

Faculty of Medicine, Department of Infectious Disease

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2074thomas.clarke

 
 
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Location

 

5.40DFlowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Clarke:2017:10.1038/s41467-017-01803-x,
author = {Clarke, TB and Brown, RL and Sequeira, RL},
doi = {10.1038/s41467-017-01803-x},
journal = {Nature Communications},
pages = {1--11},
title = {The microbiota protects against respiratory infection via GM-CSF signaling},
url = {http://dx.doi.org/10.1038/s41467-017-01803-x},
volume = {8},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The microbiota promotes resistance to respiratory infection, but the mechanistic basis forthis is poorly defined. Here, we identify members of the microbiota that protect againstrespiratory infection by the major human pathogens Streptococcus pneumoniae and Klebsiellapneumoniae. We show that the microbiota enhances respiratory defenses viagranulocyte–macrophage colony-stimulating factor (GM-CSF) signaling, which stimulatespathogen killing and clearance by alveolar macrophages through extracellular signalregulatedkinase signaling. Increased pulmonary GM-CSF production in response to infectionis primed by the microbiota through interleukin-17A. By combining models of commensalcolonization in antibiotic-treated and germ-free mice, using cultured commensals from theActinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria phyla, we found that potentNod-like receptor-stimulating bacteria in the upper airway (Staphylococcus aureus and Staphylococcusepidermidis) and intestinal microbiota (Lactobacillus reuteri, Enterococcus faecalis,Lactobacillus crispatus and Clostridium orbiscindens) promote resistance to lung infectionthrough Nod2 and GM-CSF. Our data reveal the identity, location, and properties of bacteriawithin the microbiota that regulate lung immunity, and delineate the host signaling axis theyactivate to protect against respiratory infection.
AU  - Clarke,TB
AU  - Brown,RL
AU  - Sequeira,RL
DO  - 10.1038/s41467-017-01803-x
EP  - 11
PY  - 2017///
SN  - 2041-1723
SP  - 1
TI  - The microbiota protects against respiratory infection via GM-CSF signaling
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-017-01803-x
UR  - https://www.nature.com/articles/s41467-017-01803-x
UR  - http://hdl.handle.net/10044/1/53959
VL  - 8
ER  -
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