Abstract
Historically, knowledge of human host–enteric pathogen interactions has been elucidated from studies using cancer cells, animal models, clinical data, and occasionally, controlled human infection models. Although much has been learned from these studies, an understanding of the complex interactions between human viruses and the human intestinal epithelium was initially limited by the lack of nontransformed culture systems, which recapitulate the relevant heterogenous cell types that comprise the intestinal villus epithelium. New investigations using multicellular, physiologically active, organotypic cultures produced from intestinal stem cells isolated from biopsies or surgical specimens provide an exciting new avenue for understanding human specific pathogens and revealing previously unknown host–microbe interactions that affect replication and outcomes of human infections. Here, we summarize recent biologic discoveries using human intestinal organoids and human enteric viral pathogens.
Highlights
Human intestinal organoids (HIOs), called enteroids, are cultures derived from stem cells in intestinal biopsies or surgical tissues (Figure 1b)
Differentiation of induced pluriporipotent stem cells (iPSCs) into into organoids results in epithelial associated mesenchyme; these cultures organoids results in epithelial cellscells associated withwith mesenchyme; these cultures cancan be be infected with human pathogens including rotavirus
Enterovirus 11 infection of HIOs induces significant damage of the epithelium with reorganization of tight junctions [46,47]. These results demonstrate that HIOs model early stages of enterovirus infections of the human intestinal epithelium and may allow study of how these viruses reach secondary sites of infection where more severe pathologies can develop
Summary
The human gastrointestinal tract is a complex organ that functions as a barrier, absorbs nutrients, and responds to mcrobes. The luminal surface of the small intestine is populated with villi that contain a polarized epithelial layer of different cell types including enterocytes, enteroendocrine cells, tuft cells, goblet cells, and Paneth cells. These cells differentiate from progenitor Lgr5+ stem cells located at the base of intestinal crypts [1]. Distinct regions of the intestine (duodenum, jejunum and ileum, proximal and distal colon) perform unique physiologic functions and demonstrate segment-specificity in terms of transport, protein expression, and interactions with pathogens
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