Imperial College London

DrThomasClarke

Faculty of MedicineDepartment of Medicine

Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2074thomas.clarke

 
 
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Location

 

5.40CFlowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Zhang:2009:10.1172/JCI36731,
author = {Zhang, Z and Clarke, TB and Weiser, JN},
doi = {10.1172/JCI36731},
journal = {J Clin Invest},
pages = {1899--1909},
title = {Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice.},
url = {http://dx.doi.org/10.1172/JCI36731},
volume = {119},
year = {2009}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Microbial colonization of mucosal surfaces may be an initial event in the progression to disease, and it is often a transient process. For the extracellular pathogen Streptococcus pneumoniae studied in a mouse model, nasopharyngeal carriage is eliminated over a period of weeks and requires cellular rather than humoral immunity. Here, we demonstrate that primary infection led to TLR2-dependent recruitment of monocyte/macrophages into the upper airway lumen, where they engulfed pneumococci. Pharmacologic depletion of luminal monocyte/macrophages by intranasal instillation of liposomal clodronate diminished pneumococcal clearance. Efficient clearance of colonization required TLR2 signaling to generate a population of pneumococcal-specific IL-17-expressing CD4+ T cells. Depletion of either IL-17A or CD4+ T cells was sufficient to block the recruitment of monocyte/macrophages that allowed for effective late pneumococcal clearance. In contrast with naive mice, previously colonized mice showed enhanced early clearance that correlated with a more robust influx of luminal neutrophils. As for primary colonization, these cellular responses required Th17 immunity. Our findings demonstrate that monocyte/macrophages and neutrophils recruited to the mucosal surface are key effectors in clearing primary and secondary bacterial colonization, respectively.
AU - Zhang,Z
AU - Clarke,TB
AU - Weiser,JN
DO - 10.1172/JCI36731
EP - 1909
PY - 2009///
SP - 1899
TI - Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice.
T2 - J Clin Invest
UR - http://dx.doi.org/10.1172/JCI36731
UR - https://www.ncbi.nlm.nih.gov/pubmed/19509469
VL - 119
ER -