Modulation of respiratory dendritic cells during Klebsiella pneumonia infection

Abstract

Background: Klebsiella pneumoniae is a leading cause of severe hospital-acquired respiratory tract infections anddeath 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 DCsubsets after intratracheal Klebsiella pneumonia infection.Results: Data indicate that pDCs and MoDC were markedly elevated in the post acute pneumonia phase whencompared to mock-infected controls. Analysis of draining mediastinal lymph nodes revealed a rapid increase ofactivated CD103+ DC, CD11b+ DC and MoDC within 48 h post infection. Lung pDC identification during bacterialpneumonia was confirmed by extended phenotyping for 120G8, mPDCA-1 and Siglec-H expression and bydemonstration of high Interferon-alpha producing capacity after cell sorting. Cytokine expression analysis ofex 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 toCD11c+ MHC-class IIlow cells indicating distinct functional roles. Antigen-specific naive CD4+ T cell stimulatorycapacity of purified respiratory DC subsets was analysed in a model system with purified ovalbumin T cell receptortransgenic naive CD4+ responder T cells and respiratory DC subsets, pulsed with ovalbumin and matured withKlebsiella pneumoniae lysate. CD103+ DC and CD11b+ DC subsets represented the most potent naive CD4+ Thelper cell activators.Conclusion: These results provide novel insight into the activation of respiratory DC subsets during Klebsiellapneumonia infection. The detection of increased respiratory pDC numbers in bacterial pneumonia may indicatepossible novel pDC functions with respect to lung repair and regeneration.