Investigating tracheal repair and remodeling following influenza infection 2261104

Abstract

Abstract Introduction The airway epithelium forms a critical barrier against inhaled pathogens and toxins, requiring rapid and coordinated repair following injury to maintain barrier integrity. In the distal lung, crosstalk macrophage-epithelial cell crosstalk is essential for alveolar repair after viral infection; however, the role of these interactions the proximal airways like the trachea remains unclear. Using a mouse model of influenza A virus (IAV) infection, we seek to define epithelial repair dynamics and determine the role of macrophages in coordinating tracheal regeneration. In addition to promoting repair, inflammatory responses to tissue injury and infection can lead to maladaptive remodeling, potentially predisposing the airways to disease. We hypothesize that IAV infection triggers macrophage-driven remodeling in the trachea, altering tissue composition and increasing susceptibility to allergic airway disease (AAD). Methods We use a mouse model of IAV infection to define epithelial repair dynamics and determine the role of macrophages in tracheal remodeling. Experiments incorporate transcriptomics, immunofluorescence microscopy, and flow cytometry to assess cellular composition, measure epithelial proliferation, and uncover macrophage—epithelial interactions. To test whether post-IAV remodeling enhances AAD susceptibility, we employ an IAV and allergic airway dual challenge model. Results Preliminary data reveal transcriptional alterations, macrophage accumulation, and expansion of epithelial stem and progenitor populations in the trachea following IAV infection, features consistent with active tissue remodeling. Ongoing work aims to elucidate how macrophages orchestrate epithelial repair and whether post-viral tissue reprogramming promotes AAD susceptibility. Conclusion Defining how macrophages regulate epithelial repair and remodeling in the trachea will advance understanding of immune—epithelial communication and reveal mechanisms linking viral infection to chronic airway disease. Funding Source NIH # R35GM150816, NIH # TL1TR002543 Topic Categories Mucosal and Regional Immunology (MUC)