Abstract Rationale The polymeric immunoglobulin receptor (pIgR) mediates the transcytosis of polymeric IgA across epithelial cells, maintaining mucosal immune defense. While we have shown that pIgR-deficient (pIgR−/−) mice have altered mucosal immunity in the lungs and spontaneously develop chronic obstructive pulmonary disease (COPD)-like remodeling, the role of airway mucosal immunity in influenza A virus (IAV) infection and post-viral lung disease remains incompletely undefined. Methods Wild-type (WT) and pIgR-deficient (pIgR−/−) mice were intranasally infected with influenza A virus strain A/PR/8/34 at 200 and 1000TCID50 to model acute viral lung infection and post-viral lung disease, respectively. Body weight was monitored daily. Following IAV infection, bronchoalveolar lavage (BAL) fluid was analyzed for inflammatory cell counts, and lung tissues were assessed for viral load, histopathology and collagen deposition. Additionally, lung inflammatory cell infiltration and soluble/insoluble collagen content were assessed using flow cytometry and the Sircol™ Collagen Assay Kit, respectively. Results Although IAV infection decreased pIgR expression in lungs of WT mice, no significant differences were observed between pIgR−/− and WT mice in terms of weight loss, number and proportion of inflammatory cells in BAL fluid, lung tissues viral load, or acute lung injury scores at 5 and 10 days post-IAV infection. However, at 8 weeks post-IAV infection, the absolute number and proportion of B cells and natural killer (NK) cells in lung tissues were notably downregulated in pIgR−/− mice. Furthermore, pIgR−/− mice exhibited a trend toward increased collagen accumulation in lung tissues. Conclusions IAV infection impairs the airway mucosal immune barrier by reducing pIgR expression. Secretory IgA deficiency, resulting from pIgR ablation, might contribute to dysregulated B and NK cell homeostasis and promote post-viral fibrotic remodeling. This abstract is funded by: Department of Veterans Affairs grant 2 l01 BX002378
Zeng et al. (Fri,) studied this question.