Modulation of respiratory dendritic cells during Klebsiella pneumonia infection

Respiratory Research

Susanne Herold³  Nelli Baal²  Gregor Bein²  Jürgen Lohmeyer³  Gabriela Michel²  Achim D Gruber¹  Olivia Kershaw¹  Andreas Wachtendorf²  Anne Lippitsch²  Sabine Kranz²  Holger Hackstein² 

[1] Department of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, 14163, Berlin, Germany;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;Department of Internal Medicine II, Klinikstrasse 33, Berlin, Germany

关键词: Plasmacytoid dendritic cells;    Pneumonia;    Klebsiella pneumonia;   

Others  :  792801
DOI  :  10.1186/1465-9921-14-91

 received in 2013-02-04, accepted in 2013-09-13,  发布年份 2013

【 摘 要 】

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 II^low 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.

【 授权许可】

   
2013 Hackstein et al.; licensee BioMed Central Ltd.

【 图 表 】

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