title: Nasopharyngeal colonization with Streptococcus pneumoniae triggers dendritic cell dependent antibody responses against invasive disease in mice.
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+/DTRmice, 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.
authors.affiliation: Department of Experimental Pneumology, Hannover School of Medicine, Hannover, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Dommaschk
authors.affiliation: Department of Experimental Pneumology, Hannover School of Medicine, Hannover, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Ding
authors.affiliation: Department of Experimental Pneumology, Hannover School of Medicine, Hannover, Germany.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Tort Tarres
authors.affiliation: Department of Experimental Pneumology, Hannover School of Medicine, Hannover, Germany.
authors.forename: Lara F
authors.initials: LF
authors.lastname: Bittersohl
authors.affiliation: Department of Experimental Pneumology, Hannover School of Medicine, Hannover, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Maus
authors.affiliation: Department of Experimental Pneumology, Hannover School of Medicine, Hannover, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stolper
authors.affiliation: Institute of Pathology, Hannover School of Medicine, Hannover, Germany.|German Center for Lung Research, partner site BREATH, Hannover, Germany.
authors.forename: Danny
authors.initials: D
authors.lastname: Jonigk
authors.affiliation: Institute of Pathology, Hannover School of Medicine, Hannover, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Braubach
authors.affiliation: Institute of Pathology, Hannover School of Medicine, Hannover, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Lippmann
authors.affiliation: Clinic for Pneumology, Hannover School of Medicine, Hannover, Germany.|German Center for Lung Research, partner site BREATH, Hannover, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.affiliation: Department of Experimental Pneumology, Hannover School of Medicine, Hannover, Germany.|German Center for Lung Research, partner site BREATH, Hannover, Germany.
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Maus
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000382:microbiology / Q000502:physiology*; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009305:Nasopharynx / Q000276:immunology* / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000276:immunology*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3
keywords: Colonization; Dendritic cell; NALT; Nasopharynx; S. pneumoniae