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 4

AEC GM-CSF is required for CD103+ DC activation and migration to draining MLNs under steady-state conditions and upon PR8 infection.

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AEC GM-CSF is required for CD103+ DC activation and migration to drainin...
(A and B) WT, Gm-csf–/–, SPC-GM, WT→Gm-csf–/–, and Gm-csf–/–→WT mice were PR8 infected, and the fractions of CD11b+ DCs (A) and CD103+ DCs (B) in MLNs were quantified by flow cytometry using the gating strategy in C (red gates, CD103+ DCs; blue gates, CD11b+ DCs). (D) Migratory CD103+ DCs from LH of WT mice were additionally stained for IV NP or control IgG at 5 dpi. Representative FACS plot depicts the NP+ fraction of CD45+CD11c+MHCIIhiCD103+ DCs. (E) Comparative flow cytometric quantification of CD80 and CD86 expression on lung and MLN CD103+ DCs after PR8 infection. Values are given as mean intensities ×1,000 of PE (CD80) and PE-Cy7 (CD86) fluorescence. Data are mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.005.