TY - JOUR
T1 - Modeling host-pathogen interactions in the context of the microenvironment
T2 - Three-dimensional cell culture comes of age
AU - Barrila, Jennifer
AU - Crabbé, Aurélie
AU - Yang, Jiseon
AU - Franco, Karla
AU - Nydam, Seth D.
AU - Forsyth, Rebecca J.
AU - Davis, Richard R.
AU - Gangaraju, Sandhya
AU - Ott, C. Mark
AU - Coyne, Carolyn B.
AU - Bissell, Mina J.
AU - Nickerson, Cheryl
N1 - Publisher Copyright: © 2018 American Society for Microbiology. All Rights Reserved.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
KW - 3-D
KW - 3D
KW - Gut-on-a-chip
KW - Host-microbe interaction
KW - Host-pathogen interactions
KW - Mechanotransduction
KW - Organ-on-a-chip
KW - Organoid
KW - RWV
KW - Rotating wall vessel
UR - http://www.scopus.com/inward/record.url?scp=85055617337&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055617337&partnerID=8YFLogxK
U2 - 10.1128/IAI.00282-18
DO - 10.1128/IAI.00282-18
M3 - Article
C2 - 30181350
SN - 0019-9567
VL - 86
JO - Infection and immunity
JF - Infection and immunity
IS - 11
M1 - e00282-18
ER -