Abstract
Nasopharyngeal colonization with Streptococcus pneumoniae (Spn) is an essential precondition to develop pneumococcal pneumonia. At the same time, it has also been shown to mount adaptive immune responses against Spn in mice and humans. Until now, the cellular response of the nasopharyngeal compartment, including the nasal-associated lymphoid tissue (NALT), to pneumococcal colonization and its importance for developing adaptive immune responses is poorly defined. We here show that single and even more so repetitive nasopharyngeal colonization triggered Spn-specific antibody responses in mice conferring protection against invasive pneumococcal disease (IPD). Repetitively colonized mice responded with substantial expansion of the dendritic cell (DC) compartment in nasopharyngeal tissue and NALT, along with elevated PspA-specific IgA, IgG1 and IgG2a antibody titers in plasma as well as nasal wash fluids and nasopharyngeal tissue supernatants. Relative to WT mice, both Diphtheria toxin- induced depletion of DCs in previously colonized chimeric zDC+/DTR mice and colonization of Flt3LKO mice led to significantly diminished antibody titers, as well as impaired protective immunity against IPD. Collectively, the data reveal a central role for DCs of the nasopharyngeal compartment to mediate anti-pneumococcal mucosal immune responses after colonization with Spn and hence protection against IPD in mice. These data may contribute to improve our understanding of the highly specialized nasopharyngeal/NALT compartment to expand the application of novel nasopharyngeal vaccination strategies against pneumococcal diseases in humans.
- Copyright ©the authors 2016
