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

Abstract

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.

Pseudomonas aeruginosacytochrome P450 CYP168A1 is a fatty acid hydroxylase that metabolizes arachidonic acid to the vasodilator 19-HETE

“…In general terms, the adaption of P. aeruginosa CYP168A1 to metabolize arachidonic acid to 18-, 19-, and nominally 20-HETE may reflect a burgeoning ability of the pathogen to modulate the immune response of the host organism in order to make the lung environment more palatable for colonization. A hallmark of pathogen success as a parasite is the ability for it be able to “communicate” with the host organism through the production of proteins and small molecule metabolites that have the ability to modulate the immune response and/or improve the characteristics of the host environment in order to permit pathogen growth and replication (109, 110). P. aeruginosa may accomplish this through its metabolism of arachidonic acid to metabolites, such as 18-, 19,- and 20-HETE, that provide important physiological functions.…”

Pseudomonas aeruginosa cytochrome P450 CYP168A1 is a fatty acid hydroxylase that metabolizes arachidonic acid to the vasodilator 19-HETE

“…In general terms, the adaption of P. aeruginosa CYP168A1 to metabolize arachidonic acid to 18-, 19-, and nominally 20-HETE may reflect a burgeoning ability of the pathogen to modulate the immune response of the host organism in order to make the lung environment more palatable for colonization. A hallmark of pathogen success as a parasite is the ability for it be able to "communicate" with the host organism through the production of proteins and small molecule metabolites that can modulate the immune response and/or improve the characteristics of the host environment in order to permit pathogen growth and replication (109,110). P. aeruginosa may accomplish this through its metabolism of arachidonic acid to metabolites, such as 18-, 19,-and 20-HETE, that provide important physiological functions.…”

Bacterial Species Associated with Highly Allergenic Plant Pollen Yield a High Level of Endotoxins and Induce Chemokine and Cytokine Release from Human A549 Cells

“…Airborne antigens such as pollen-associated bacteria interact with or penetrate into the epithelial barrier of the respiratory tract; both innate and adaptive immune responses can be triggered [22,23]. The first step in this signal cascade is a contact-dependent interaction of molecular patterns such as bacterial LPS or LTA with recognition receptors on cells of the epithelial surface or directly with immune cells [24]. Cell surface bound toll-like receptors (TLRs) as well as C-type lectin receptors (CLRs) detect LPS patterns on Gram-negative bacteria [24][25][26].…”

“…The first step in this signal cascade is a contact-dependent interaction of molecular patterns such as bacterial LPS or LTA with recognition receptors on cells of the epithelial surface or directly with immune cells [24]. Cell surface bound toll-like receptors (TLRs) as well as C-type lectin receptors (CLRs) detect LPS patterns on Gram-negative bacteria [24][25][26]. The result of this receptor-ligand crosstalk is a release of pro-inflammatory mediators not only by professional immune cells but also by non-professional immune cells such as epithelial cells.…”