title: Modulation of respiratory dendritic cells during Klebsiella pneumonia infection.
abstract: BACKGROUND
  Klebsiella pneumoniae is a leading cause of severe hospital-acquired respiratory tract infections and death but little is known regarding the modulation of respiratory dendritic cell (DC) subsets. Plasmacytoid DC (pDC) are specialized type 1 interferon producing cells and considered to be classical mediators of antiviral immunity.
  
  
  METHODS
  By using multiparameter flow cytometry analysis we have analysed the modulation of respiratory DC subsets after intratracheal Klebsiella pneumonia infection.
  
  
  RESULTS
  Data indicate that pDCs and MoDC were markedly elevated in the post acute pneumonia phase when compared to mock-infected controls. Analysis of draining mediastinal lymph nodes revealed a rapid increase of activated CD103+ DC, CD11b+ DC and MoDC within 48 h post infection. Lung pDC identification during bacterial pneumonia was confirmed by extended phenotyping for 120G8, mPDCA-1 and Siglec-H expression and by demonstration of high Interferon-alpha producing capacity after cell sorting. Cytokine expression analysis of ex vivo-sorted respiratory DC subpopulations from infected animals revealed elevated Interferon-alpha in pDC, elevated IFN-gamma, IL-4 and IL-13 in CD103+ DC and IL-19 and IL-12p35 in CD11b+ DC subsets in comparison to CD11c+ MHC-class IIlow cells indicating distinct functional roles. Antigen-specific naive CD4+ T cell stimulatory capacity of purified respiratory DC subsets was analysed in a model system with purified ovalbumin T cell receptor transgenic naive CD4+ responder T cells and respiratory DC subsets, pulsed with ovalbumin and matured with Klebsiella pneumoniae lysate. CD103+ DC and CD11b+ DC subsets represented the most potent naive CD4+ T helper cell activators.
  
  
  CONCLUSIONS
  These results provide novel insight into the activation of respiratory DC subsets during Klebsiella pneumonia infection. The detection of increased respiratory pDC numbers in bacterial pneumonia may indicate possible novel pDC functions with respect to lung repair and regeneration.
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University Giessen, Member of the German Center for Lung Research (DZL), Langhansstr, 7, D-35392, Giessen, Germany. Holger.Hackstein@immunologie.med.uni-giessen.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Hackstein
authors.forename: Sabine
authors.initials: S
authors.lastname: Kranz
authors.forename: Anne
authors.initials: A
authors.lastname: Lippitsch
authors.forename: Andreas
authors.initials: A
authors.lastname: Wachtendorf
authors.forename: Olivia
authors.initials: O
authors.lastname: Kershaw
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.forename: Gabriela
authors.initials: G
authors.lastname: Michel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Lohmeyer
authors.forename: Gregor
authors.initials: G
authors.lastname: Bein
authors.forename: Nelli
authors.initials: N
authors.lastname: Baal
authors.forename: Susanne
authors.initials: S
authors.lastname: Herold
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D060890:B7-H1 Antigen / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D066298:In Vitro Techniques; D039001:Integrin alpha Chains / Q000378:metabolism; D007710:Klebsiella Infections / Q000276:immunology / Q000473:pathology*; D007711:Klebsiella pneumoniae; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D012137:Respiratory System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D060890:B7-H1 Antigen; D039481:CD11b Antigen; D016207:Cytokines; D039001:Integrin alpha Chains; C091367:alpha E integrins
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