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

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.; Maurelli, Anthony T.

doi:10.1128/IAI.00282-18

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

Journal Article · Tue Sep 04 00:00:00 EDT 2018 · Infection and Immunity

DOI:https://doi.org/10.1128/IAI.00282-18· OSTI ID:1580337

^[1]; ^[2]; Yang, Jiseon ^[1]; Franco, Karla ^[1]; Nydam, Seth D. ^[1]; Forsyth, Rebecca J. ^[1]; Davis, Richard R. ^[1]; Gangaraju, Sandhya ^[1]; Ott, C. Mark ^[3]; ^[4]; Bissell, Mina J. ^[5]; ^[1]; Maurelli, Anthony T. ^[6]

Arizona State Univ., Tempe, AZ (United States)
Ghent Univ., Ghent (Belgium)
NASA Johnson Space Center, Houston, TX (United States)
Univ. of Pittsburgh, Pittsburgh, PA (United States)
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Univ. of Florida, Gainesville, FL (United States)

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). Here, 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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1580337

Journal Information:: Infection and Immunity, Journal Name: Infection and Immunity Journal Issue: 11 Vol. 86; ISSN 0019-9567

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

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