Eur J Immunol. 2017 Mar;47(3):540-551. doi: 10.1002/eji.201646700. Epub 2017 Feb 1.

Nasopharyngeal colonization with Streptococcus pneumoniae triggers dendritic cell dependent antibody responses against invasive disease in mice.

Dommaschk A1, Ding N1, Tort Tarres M1, Bittersohl LF1, Maus R1, Stolper J1, Jonigk D2,3, Braubach P2, Lippmann T2, Welte T4,3, Maus UA1,3.

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Abstract

Nasopharyngeal colonization with Streptococcus pneumoniae (Spn) is an important precondition for the development of pneumococcal pneumonia. At the same time, nasopharyngeal colonization with Spn has been shown to mount adaptive immune responses against Spn in mice and humans. Cellular responses of the nasopharyngeal compartment, including the nasal-associated lymphoid tissue, to pneumococcal colonization and their importance for developing adaptive immune responses are poorly defined. We show that nasopharyngeal colonization with S. pneumoniae led to substantial expansion of dendritic cells (DCs) both in nasopharyngeal tissue and nasal-associated lymphoid tissue of mice. Depletion of DCs achieved by either diphtheria toxin (DT) treatment of chimeric zDC+/DTR mice, or by use of FMS-like tyrosine kinase 3 ligand (Flt3L) KO mice exhibiting congenitally reduced DC pool sizes, significantly diminished antibody responses after colonization with Spn, along with impaired protective immunity against invasive pneumococcal disease. Collectively, the data show that classical DCs contribute to pneumococcal colonization induced adaptive immune responses against invasive pneumococcal disease in two different mouse models. These data may be useful for future nasopharyngeal vaccination strategies against pneumococcal diseases in humans.

© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS:

Colonization; Dendritic cell; NALT; Nasopharynx; S. pneumoniae

PMID: 28101913