Modeling Host-Pathogen Interactions in the Context of the Microenvironment: Three-Dimensional Cell Culture Comes of Age

Tissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important insight into understanding host-pathogen inte...

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Vydané v:Infection and immunity Ročník 86; číslo 11
Hlavní autori: Barrila, Jennifer, Crabbé, Aurélie, Yang, Jiseon, Franco, Karla, Nydam, Seth D, Forsyth, Rebecca J, Davis, Richard R, Gangaraju, Sandhya, Ott, C Mark, Coyne, Carolyn B, Bissell, Mina J, Nickerson, Cheryl A
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 01.11.2018
Predmet:
Cellular Microenvironment
History, 20th Century
History, 21st Century
Host-Pathogen Interactions
Humans
Intestinal Mucosa - physiology
Models, Biological
Organ Culture Techniques - history
Organ Culture Techniques - methods
Organoids
Tissue Engineering - history
Tissue Engineering - methods
RWV
3D
host-pathogen interactions
mechanotransduction
rotating wall vessel
gut-on-a-chip
3-D
organ-on-a-chip
host-microbe interaction
organoid
ISSN:1098-5522, 1098-5522
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Shrnutí:Tissues and organs provide the structural and biochemical landscapes upon which microbial pathogens and commensals function to regulate health and disease. While flat two-dimensional (2-D) monolayers composed of a single cell type have provided important insight into understanding host-pathogen interactions and infectious disease mechanisms, these reductionist models lack many essential features present in the native host microenvironment that are known to regulate infection, including three-dimensional (3-D) architecture, multicellular complexity, commensal microbiota, gas exchange and nutrient gradients, and physiologically relevant biomechanical forces (e.g., fluid shear, stretch, compression). A major challenge in tissue engineering for infectious disease research is recreating this dynamic 3-D microenvironment (biological, chemical, and physical/mechanical) to more accurately model the initiation and progression of host-pathogen interactions in the laboratory. Here we review selected 3-D models of human intestinal mucosa, which represent a major portal of entry for infectious pathogens and an important niche for commensal microbiota. We highlight seminal studies that have used these models to interrogate host-pathogen interactions and infectious disease mechanisms, and we present this literature in the appropriate historical context. Models discussed include 3-D organotypic cultures engineered in the rotating wall vessel (RWV) bioreactor, extracellular matrix (ECM)-embedded/organoid models, and organ-on-a-chip (OAC) models. Collectively, these technologies provide a more physiologically relevant and predictive framework for investigating infectious disease mechanisms and antimicrobial therapies at the intersection of the host, microbe, and their local microenvironments.
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ISSN:1098-5522
1098-5522
DOI:10.1128/IAI.00282-18