Alveolar Overexpression of the Polymeric Immunoglobulin Receptor in the Inflamed Lung as a Novel Mechanism for Antibody-mediated Immune Exclusion of Bacterial Pathogens

Community-acquired pneumonia caused by bacterial pathogens represents a major comorbidity in individuals with chronic respiratory diseases. In order to improve our understanding regarding potential alterations in the immune response to bacterial pathogens in hosts with preexisting conditions in the lung, we performed Streptococcus pneumoniae infections in mice with established CD4⁺ T cell-mediated lung inflammation. Despite increased pulmonary leak and in direct contrast to our expectation, mice with preexisting lung inflammation showed improved anti-pneumococcal resistance. This became evident by a better control of bacterial growth in the airways and prolonged survival of infected mice. Enhanced phagocytic activity of alveolar macrophages as an underlying mechanism for anti-pneumococcal resistance could be excluded. Whole genome transcriptional profiling of lung tissue and comprehensive analysis of the bronchioalveolar lavage (BAL) protein composition from diseased mice and healthy controls revealed a striking overrepresentation of the polymeric immunoglobulin receptor (pIgR) in the inflamed lung. Elevated pIgR expression was localized to alveolar epithelial cells and resulted in increased mucosal transport of secretory IgM and IgA into the bronchioalveolar space of diseased mice. sIgM and sIgA binding assays revealed increased pneumococcal binding by secretory antibodies present in the BAL fluid of mice with preexisting lung inflammation. In conclusion, we propose inflammation-induced overexpression of pIgR in alveolar epithelial cells as a novel mechanism for antibody-mediated immune exclusion of bacterial pathogens that efficiently prevents bacterial adhesion to and penetration of the pre-injured airway epithelium.