Host and Pathogen Communication in the Respiratory Tract: Mechanisms and Models of a Complex Signaling Microenvironment

Chronic lung diseases are a leading cause of morbidity and mortality across the globe, encompassing a diverse range of conditions from infections with pathogenic microorganisms to underlying genetic disorders. The respiratory tract represents an active interface with the external environment having the primary immune function of resisting pathogen intrusion and maintaining homeostasis in response to the myriad of stimuli encountered within its microenvironment. To perform these vital functions and prevent lung disorders, a chemical and biological cross-talk occurs in the complex milieu of the lung that mediates and regulates the numerous cellular processes contributing to lung health. In this review, we will focus on the role of cross-talk in chronic lung infections, and discuss how different cell types and signaling pathways contribute to the chronicity of infection(s) and prevent effective immune clearance of pathogens. In the lung microenvironment, pathogens have developed the capacity to evade mucosal immunity using different mechanisms or virulence factors, leading to colonization and infection of the host; such mechanisms include the release of soluble and volatile factors, as well as contact dependent (juxtracrine) interactions. We explore the diverse modes of communication between the host and pathogen in the lung tissue milieu in the context of chronic lung infections. Lastly, we review current methods and approaches used to model and study these host-pathogen interactions in vitro, and the role of these technological platforms in advancing our knowledge about chronic lung diseases.