Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 119, Issue 7, Pages 1899-1909Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI36731
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Funding
- US Public Health Service [A144231, A138446]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI038446, R21AI044231, R01AI044231] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK050306] Funding Source: NIH RePORTER
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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.
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