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J Clin Invest. 2009 Jul;119(7):1899-909. doi: 10.1172/JCI36731. Epub 2009 Jun 8.

Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice.

Author information

1
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6076, USA.

Abstract

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.

PMID:
19509469
PMCID:
PMC2701860
DOI:
10.1172/JCI36731
[Indexed for MEDLINE]
Free PMC Article

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