Mimicking the host and its microenvironmentin vitrofor studying mucosal infections byPseudomonas 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? In order to address this question, it is essential to thoroughly understand the dynamic interplay between the host microenvironment and P. aeruginosa. Therefore, using modeI 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.

A three-dimensional intestinal tissue model reveals factors and small regulatory RNAs important for colonization with Campylobacter jejuni

“…In line with our results for C. jejuni and the tissue-engineered 3D model, various other 3D models including those cultured in the rotating wall vessel bioreactor (RWV) or organs-on-achip are promising new tools for infection research and have been applied to study a variety of pathogens, such as S. Typhimurium, Pseudomonas aeruginosa, or Mycobacterium tuberculosis [84][85][86][87][88][89]. For example, 3D models grown in the RWV successfully recapitulated infection outcomes, such as SPI-1 independent invasion of host cells by S. Typhimurium [84], as previously observed in vivo [90].…”

Is There a Space-Based Technology Solution to Problems with Preclinical Drug Toxicity Testing?

“…NASA suspension culture techniques reverse much of the problematic de-differentiation of cells observed during other forms of tissue culture (35–38). The technology has been applied broadly to diverse cell types including cancer cells, prostate, kidney, micro-organisms, biofilms, and plants, to name a few (36,39,40). …”

Lung Stem Cells in the Epithelium and Vasculature

“…In addition to repopulation assays, it has also been suggested that recellularized acellular scaffolds could also be used for studying infectious diseases (Crabbé et al 2014 ) and used as models for cancer development (Mishra et al 2012 ). Thus, studies to date have likely only begun to demonstrate the utility of acellular tissue as ex vivo models of disease which more closely recapitulate in vivo microenvironments than traditional in vitro setups.…”