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Modeling host-pathogen interactions in the context of the microenvironment : three-dimensional cell culture comes of agee

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Abstract
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.
Keywords
ROTATING-WALL VESSEL, ON-A-CHIP, ENTERICA SEROVAR TYPHIMURIUM, IN-VITRO EXPANSION, PSEUDOMONAS-AERUGINOSA ADHERENCE, INTESTINAL EPITHELIAL-CELLS, ENGINEERED CARDIAC TISSUES, DECAY-ACCELERATING FACTOR, PLURIPOTENT STEM-CELLS, FLUID SHEAR-STRESS, 3-D, 3D, RWV, rotating wall vessel, gut-on-a-chip, host-microbe interaction, host-pathogen interactions, mechanotransduction, organ-on-a-chip, organoid

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Citation

Please use this url to cite or link to this publication:

MLA
Barrila, Jennifer, et al. “Modeling Host-Pathogen Interactions in the Context of the Microenvironment : Three-Dimensional Cell Culture Comes of Agee.” INFECTION AND IMMUNITY, vol. 86, no. 11, 2018.
APA
Barrila, J., Crabbé, A., Yang, J., Franco, K., Nydam, S. D., Forsyth, R. J., … Nickerson, C. A. (2018). Modeling host-pathogen interactions in the context of the microenvironment : three-dimensional cell culture comes of agee. INFECTION AND IMMUNITY, 86(11).
Chicago author-date
Barrila, Jennifer, Aurélie Crabbé, Jiseon Yang, Karla Franco, Seth D. Nydam, Rebecca J. Forsyth, Richard R. Davis, et al. 2018. “Modeling Host-Pathogen Interactions in the Context of the Microenvironment : Three-Dimensional Cell Culture Comes of Agee.” INFECTION AND IMMUNITY 86 (11).
Chicago author-date (all authors)
Barrila, Jennifer, Aurélie Crabbé, Jiseon Yang, Karla Franco, Seth D. Nydam, Rebecca J. Forsyth, Richard R. Davis, Sandhya Gangaraju, C. Mark Ott, Carolyn B. Coyne, Mina J. Bissell, and Cheryl A. Nickerson. 2018. “Modeling Host-Pathogen Interactions in the Context of the Microenvironment : Three-Dimensional Cell Culture Comes of Agee.” INFECTION AND IMMUNITY 86 (11).
Vancouver
1.
Barrila J, Crabbé A, Yang J, Franco K, Nydam SD, Forsyth RJ, et al. Modeling host-pathogen interactions in the context of the microenvironment : three-dimensional cell culture comes of agee. INFECTION AND IMMUNITY. 2018;86(11).
IEEE
[1]
J. Barrila et al., “Modeling host-pathogen interactions in the context of the microenvironment : three-dimensional cell culture comes of agee,” INFECTION AND IMMUNITY, vol. 86, no. 11, 2018.
@article{8625284,
  abstract     = {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.},
  articleno    = {e00282-18},
  author       = {Barrila, Jennifer and Crabbé, Aurélie and Yang, Jiseon and Franco, Karla and Nydam, Seth D. and Forsyth, Rebecca J. and Davis, Richard R. and Gangaraju, Sandhya and Ott, C. Mark and Coyne, Carolyn B. and Bissell, Mina J. and Nickerson, Cheryl A.},
  issn         = {0019-9567},
  journal      = {INFECTION AND IMMUNITY},
  keywords     = {ROTATING-WALL VESSEL,ON-A-CHIP,ENTERICA SEROVAR TYPHIMURIUM,IN-VITRO EXPANSION,PSEUDOMONAS-AERUGINOSA ADHERENCE,INTESTINAL EPITHELIAL-CELLS,ENGINEERED CARDIAC TISSUES,DECAY-ACCELERATING FACTOR,PLURIPOTENT STEM-CELLS,FLUID SHEAR-STRESS,3-D,3D,RWV,rotating wall vessel,gut-on-a-chip,host-microbe interaction,host-pathogen interactions,mechanotransduction,organ-on-a-chip,organoid},
  language     = {eng},
  number       = {11},
  pages        = {28},
  title        = {Modeling host-pathogen interactions in the context of the microenvironment : three-dimensional cell culture comes of agee},
  url          = {http://dx.doi.org/10.1128/iai.00282-18},
  volume       = {86},
  year         = {2018},
}

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