Coincident airway exposure to low-potency allergen and cytomegalovirus sensitizes for allergic airway disease by viral activation of migratory dendritic cells

• DOI: 10.1371/journal.ppat.1007595
• Publication Date: 2019-03-07T18:28:16Z
• Authors: Sebastian Reuter; Niels A. W. Lemme...; Joachim Maxeiner; Jürgen Podlech; Hendrik Beckert; Kirsten Freitag; Daniel Teschner; Frederic Ries; Christian Taube; Roland Buhl; Matthias J. Redde...; Rafaela Holtappels
• Keywords: Lung Diseases; 0301 basic medicine; QH301-705.5; Ovalbumin; Medizin; Cytomegalovirus; Mice; 03 medical and health sciences; Th2 Cells; Hypersensitivity; Animals; Biology (General); Lung; Inflammation; Antigen Presentation; CD11 Antigens; Dendritic Cells; RC581-607; Allergens; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Female; Virus Activation; Immunologic diseases. Allergy; Research Article

Despite a broad cell-type tropism, cytomegalovirus (CMV) is an evidentially pulmonary pathogen. Predilection for the lungs of medical relevance in immunocompromised recipients hematopoietic cell transplantation, whom interstitial CMV pneumonia frequent and, if left untreated, fatal clinical manifestation human infection. A conceivable contribution to airway diseases other etiology issue that so far attracted little attention. As route primary infection upon host-to-host transmission early childhood involves mucosa, coincidence and exposure airborne environmental antigens almost unavoidable. For investigating possible consequences such coincidence, we established mouse model co-exposure ovalbumin (OVA) representing protein antigen inherently low allergenic potential. Accordingly, intratracheal OVA alone failed sensitize allergic disease (AAD) aerosol challenge. In contrast, at time sensitization predisposed AAD was characterized by inflammation, IgE secretion, thickening epithelia, goblet hyperplasia. This histopathology associated with T helper type 2 (Th2) transcription profile lungs, including IL-4, IL-5, IL-9, IL-25, known inducers Th2-driven AAD. These symptoms were all prevented pre-challenge depletion CD4+ cells, but not CD8+ cells. underlying mechanism, murine activated migratory CD11b+ as well CD103+ conventional dendritic cells (cDCs), which have been Th2 cytokine-driven cross-presentation, respectively. resulted enhanced uptake recruitment OVA-laden cDCs selectively draining tracheal lymph nodes presentation. We thus propose CMV, through activation can enhance potential otherwise poorly antigens.