title: Dectin-2-dependent host defense in mice infected with serotype 3 Streptococcus pneumoniae.
abstract: BACKGROUND
  Streptococcus pneumoniae, a major causative bacterial pathogen of community-acquired pneumonia, possesses a thick polysaccharide capsule. Host defense against this bacterium is mediated by activation of innate immune cells that sense bacterial components. Recently, C-type lectin receptors (CLRs) have garnered much attention in elucidating the recognition mechanism of pathogen-derived polysaccharides.
  
  
  METHODS
  In the present study, we first compared the clinical course and neutrophil accumulation in the lungs of Dectin-2 knock-out (KO) and wild type (WT) mice. Mice were infected intratracheally with a serotype 3 strain of S. pneumoniae, and S. pneumoniae bacterial engulfment by neutrophils and inflammatory cytokine and anti-pneumococcal polysaccharide-specific IgG levels were evaluated in bronchoalveolar lavage fluid (BALF). We also examined the effect of Dectin-2 deficiency on interleukin (IL)-12 production by bone marrow-derived dendritic cells (BM-DCs) stimulated with the bacterial components.
  
  
  RESULTS
  S. pneumonia-infected Dectin-2KO mice had a shorter survival time, larger bacterial burden and lower interferon gamma (IFN-γ) production in the lungs than WT mice. Although neutrophilic infiltration in the lungs was equivalent between Dectin-2KO mice and WT mice, S. pneumonia engulfment by neutrophils was attenuated in Dectin-2KO mice compared to WT mice. The anti-pneumococcal polysaccharide-specific IgG and IgG3 levels in BALF were lower in Dectin-2KO mice than in WT mice. When BM-DCs were stimulated with S. pneumoniae culture supernatant or its Concanavalin A (ConA)-bound fraction, IL-12 production was abrogated in Dectin-2KO mice compared to WT mice.
  
  
  CONCLUSIONS
  We demonstrated that Dectin-2 is intimately involved in the host defense against infection with a serotype 3 strain of S. pneumoniae. Dectin-2-dependent IL-12 production may contribute to IFN-γ synthesis and subsequent production of serotype-specific anti-capsular polysaccharide IgG after S. pneumoniae infection, which may promote S. pneumoniae bacterial opsonization for engulfment.
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Miyagi, Japan. nieva.divierta.vida@silk.ocn.ne.jp.|Present address: Japanese Red Cross Society, Tokyo, Japan. nieva.divierta.vida@silk.ocn.ne.jp.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Akahori
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Miyagi, Japan. miyasaka.tomomitsu@nifty.ne.jp.|Present address: Department of Pathophysiology, Tohoku Pharmaceutical University, Miyagi, Japan. miyasaka.tomomitsu@nifty.ne.jp.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyasaka
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Miyagi, Japan. natunohizanzouf42@yahoo.co.jp.|Present address: Ibaraki Prefectural Hospital, Ibaraki, Japan. natunohizanzouf42@yahoo.co.jp.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Toyama
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Miyagi, Japan. ikikmsms@gmail.com.
authors.forename: Ikumi
authors.initials: I
authors.lastname: Matsumoto
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Miyagi, Japan. miyanna0407@gmail.com.
authors.forename: Anna
authors.initials: A
authors.lastname: Miyahara
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Miyagi, Japan. zongtong@med.tohoku.ac.jp.
authors.forename: Tong
authors.initials: T
authors.lastname: Zong
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Miyagi, Japan. ishii-k@med.tohoku.ac.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan. ykinjo@niid.go.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kinjo
authors.affiliation: Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan. ym46@niid.go.jp.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan. saijo@faculty.chiba-u.jp.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Saijo
authors.affiliation: Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan. iwakura@rs.tus.ac.jp.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Miyagi, Japan. kawakami@med.tohoku.ac.jp.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity / Q000276:immunology; D001854:Bone Marrow Cells / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000378:metabolism; D037181:Lectins, C-Type / Q000172:deficiency / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000378:metabolism; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D018925:Chemokines; D018836:Inflammation Mediators; D037181:Lectins, C-Type; C445340:dectin-2, mouse; D018664:Interleukin-12; D007371:Interferon-gamma