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Modulation of respiratory dendritic cells during Klebsiella pneumonia infection

Hackstein, Holger ; Kranz, Sabine ; Lippitsch, Anne ; Wachtendorf, Andreas ; Kershaw, Olivia ; Gruber, Achim D ; Michel, Gabriela ; Lohmeyer, J├╝rgen ; Bein, Gregor ; Baal, Nelli ; Herold, Susanne

Originalveröffentlichung: (2013) Respiratory Research 14(1):91 doi:10.1186/1465-9921-14-91
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URN: urn:nbn:de:hebis:26-opus-104150

Freie Schlagwörter (Englisch): Klebsiella pneumonia , Pneumonia , Plasmacytoid dendritic cells
Sammlung: Open Access - Publikationsfonds
Universität Justus-Liebig-Universit├Ąt Gie├čen
Fachgebiet: Medizin
DDC-Sachgruppe: Medizin
Dokumentart: Aufsatz
Sprache: Englisch
Erstellungsjahr: 2013
Publikationsdatum: 06.12.2013
Kurzfassung auf Englisch: 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.
Method: 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.
Conclusion: 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.
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