Abstract
Nasopharyngeal colonization with S. pneumoniae (Spn) has been shown to mount adaptive immune responses against Spn in mice and humans. However, the cellular response of the nasopharyngeal compartment, including the nasal-associated lymphoreticular tissue (NALT), to pneumococcal colonization is poorly defined. We show that intranasal administration of Spn into mice resulted in nasopharyngeal colonization for at least 28 days, and triggered a substantial Spn-specific antibody response. Single colonization conferred protection against highly invasive Spn in mice, which was even more pronounced in repetitively colonized mice. Expansion of both the T cell and dendritic cell (DC) subset compartment was observed in the nasopharyngeal tissue and in the NALT of mice colonized with Spn. Diphtheria toxin-induced depletion of DCs in previously colonized zDC+/DTR chimeric mice led to substantially diminished antibody responses and impaired protective immunity against invasive pneumococcal disease. Collectively, the data reveal a central role for DCs of the nasopharyngeal compartment to regulate adaptive immune responses and protection against IPD in mice colonized with Spn.
- Copyright ©ERS 2015