Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice.
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.
Zhang
Zhe
Z
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6076, USA.
Clarke
Thomas B
TB
Weiser
Jeffrey N
JN
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004002:Clodronic Acid / Q000008:administration & dosage; D020381:Interleukin-17 / Q000502:physiology*; D008081:Liposomes; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology; D011008:Pneumococcal Infections / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000502:physiology
D020381:Interleukin-17; D008081:Liposomes; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D004002:Clodronic Acid