Mimicking the host and its microenvironment in vitro for studying mucosal infections by Pseudomonas aeruginosa

Abstract

Why is a healthy person protected from Pseudomonas aeruginosa infections, while individuals with cystic fibrosis or damaged epithelium are particularly susceptible to this opportunistic pathogen? To address this question, it is essential to thoroughly understand the dynamic interplay between the host microenvironment and P. aeruginosa. Therefore, using model systems that represent key aspects of human mucosal tissues in health and disease allows recreating in vivo host-pathogen interactions in a physiologically relevant manner. In this review, we discuss how factors of mucosal tissues, such as apical-basolateral polarity, junctional complexes, extracellular matrix proteins, mucus, multicellular complexity (including indigenous microbiota), and other physicochemical factors affect P. aeruginosa pathogenesis and are thus important to mimic in vitro. We highlight in vitro cell and tissue culture model systems of increasing complexity that have been used over the past 35 years to study the infectious disease process of P. aeruginosa, mainly focusing on lung models, and their respective advantages and limitations. Continued improvements of in vitro models based on our expanding knowledge of host microenvironmental factors that participate in P. aeruginosa pathogenesis will help advance fundamental understanding of pathogenic mechanisms and increase the translational potential of research findings from bench to the patient's bedside.

Keywords: cell differentiation; cystic fibrosis; epithelial injury; host-pathogen interactions; microbiome; three-dimensional.

Figure 1

The lung mucosal tissue in a healthy person (A), a patient with damaged epithelium (e.g., bronchoscopy, cathether, and surgery) (B), and a cystic fibrosis patient (C). Key factors that protect a healthy host against P. aeruginosa infection (A) or that contribute to P. aeruginosa initiation of infectious disease (B and C) are depicted. While additional host factors are altered during disease, only those that have a well-documented effect on P. aeruginosa pathogenesis are presented. In addition, host factors that are changed due to infection by P. aeruginosa are not included or discussed.