Mapping Host Defense at the Respiratory Barrier

Abstract:

Immune and epithelial programs regulate the pulmonary barrier, shaping defense to infection. Their high-dimensional complexity is challenging to assess with conventional methods. To address our research questions, we therefore integrate patient data, animal pneumonia models, and advanced organotypic systems, combining functional assays with single-cell and spatial omics.

Our work identifies key mechanisms of barrier disruption in pneumonia and acute lung injury, while also defining how local immune responses contribute to early protection at mucosal surfaces. In parallel, we explore how biomechanical forces and the pulmonary glycocalyx shape host–pathogen interactions, revealing how physical and biochemical features of the tissue microenvironment influence susceptibility to infection.

Together, these findings establish the respiratory barrier as an integrated system in which immune activity, epithelial states, and tissue context collectively determine infection outcomes. This work provides a framework for understanding mucosal defense and highlights new opportunities to strengthen barrier resilience in the lung.