Cellular Effectors Mediating Th17-dependent Clearance of Pneumococcal Colonization in Mice

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

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Clodronic Acid / administration & dosage
  • Interleukin-17 / physiology*
  • Liposomes
  • Macrophages / physiology
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / physiology
  • Pneumococcal Infections / immunology*
  • Toll-Like Receptor 2 / physiology

Substances

  • Interleukin-17
  • Liposomes
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Clodronic Acid