Alveolar epithelial cells orchestrate DC function in murine viral pneumonia
Barbara Unkel, … , Juergen Lohmeyer, Susanne Herold
Barbara Unkel, … , Juergen Lohmeyer, Susanne Herold
Published September 10, 2012
Citation Information: J Clin Invest. 2012;122(10):3652-3664. https://doi.org/10.1172/JCI62139.
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Research Article Immunology

Alveolar epithelial cells orchestrate DC function in murine viral pneumonia

Abstract

Influenza viruses (IVs) cause pneumonia in humans with progression to lung failure. Pulmonary DCs are key players in the antiviral immune response, which is crucial to restore alveolar barrier function. The mechanisms of expansion and activation of pulmonary DC populations in lung infection remain widely elusive. Using mouse BM chimeric and cell-specific depletion approaches, we demonstrated that alveolar epithelial cell (AEC) GM-CSF mediates recovery from IV-induced injury by affecting lung DC function. Epithelial GM-CSF induced the recruitment of CD11b+ and monocyte-derived DCs. GM-CSF was also required for the presence of CD103+ DCs in the lung parenchyma at baseline and for their sufficient activation and migration to the draining mediastinal lymph nodes (MLNs) during IV infection. These activated CD103+ DCs were indispensable for sufficient clearance of IVs by CD8+ T cells and for recovery from IV-induced lung injury. Moreover, GM-CSF applied intratracheally activated CD103+ DCs, inducing increased migration to MLNs, enhanced viral clearance, and attenuated lung injury. Together, our data reveal that GM-CSF–dependent cross-talk between IV-infected AECs and CD103+ DCs is crucial for effective viral clearance and recovery from injury, which has potential implications for GM-CSF treatment in severe IV pneumonia.

Authors

Barbara Unkel, Katrin Hoegner, Björn E. Clausen, Peter Lewe-Schlosser, Johannes Bodner, Stefan Gattenloehner, Hermann Janßen, Werner Seeger, Juergen Lohmeyer, Susanne Herold

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Figure 5

AEC GM-CSF is required for alveolar antiviral CD8+ T cell responses and PR8 clearance from mouse lungs.

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AEC GM-CSF is required for alveolar antiviral CD8+ T cell responses and ...
(A) Absolute numbers of CD4+ and CD8+ T lymphocytes in BALF were determined by counting BALF cells and by flow cytometric quantification of the CD45+SSCloCD3+CD4+ and CD45+SSCloCD3+CD8+ fractions, respectively, after PR8 infection in WT, Gm-csf–/–, and SPC-GM mice. (B) Antigen-specific CD4+ and CD8+ T cell numbers in BALF or spleen, determined by analysis of the NPpeptide/H2-Db dextramer+ or the IFN-γ+ fraction of CD45+SSCloCD3+CD4+ and CD45+SSCloCD3+CD8+ cells, respectively, after PR8 infection (7 dpi). (C) Representative FACS plots of the IFN-γ analysis; percent values of the respective IFN-γ+ proportions are shown in each plot. (D) PR8 titers in WT, Gm-csf–/–, SPC-GM, WT→Gm-csf–/–, and Gm-csf–/–→WT mice, quantified from BALF at the indicated dpi by standard plaque assay and given as PFU/ml × log10 (detection limit, 101 PFU/ml × log10). Data are mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.005. SSC, side scatter.