We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice.
- Authors
Zhe Zhang; Clarke, Thomas B.; Weiser, Jeffrey N.; Zhang, Zhe
- 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.
- Subjects
STREPTOCOCCUS pneumoniae; MONOCYTES; MACROPHAGES; PNEUMOCOCCAL pneumonia; MICROBIAL cell cycle; NEUTROPHILS; CELL receptors; ANIMALS; DIPHOSPHONATES; INTERLEUKINS; ARTIFICIAL membranes; MICE; STREPTOCOCCAL diseases; T cells; PHYSIOLOGY; CELL physiology
- Publication
Journal of Clinical Investigation, 2009, Vol 119, Issue 7, p1899
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI36731