[HTML][HTML] Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice

Z Zhang, TB Clarke, JN Weiser - The Journal of clinical …, 2009 - Am Soc Clin Investig
Z Zhang, TB Clarke, JN Weiser
The Journal of clinical investigation, 2009Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation