Organoid culture systems to study host–pathogen interactions

Abstract

Recent advances in host-microbe interaction studies in organoid cultures have shown great promise and have laid the foundation for much more refined future studies using these systems. Modeling of Zika virus (ZIKV) infection in cerebral organoids have helped us understand its association with microcephaly. Similarly, the pathogenesis of bacterial (Helicobacter pylori, Clostridium difficile) and viral (Norovirus, Rotaviruses) infections have been precisely dissected in organoid cultures. Additionally, direct associations between microbial colonization of tissues and diseases like cancer have also been deciphered. Here we discuss the most recent and striking studies on host-microbe interactions in organoid cultures, highlighting various methods which can be used for developing microbe-organoid co-culture systems.

Potential application of cell reprogramming techniques for cancer research

“…Among the tumor suppressor genes, the status of TP53 signaling in CSCs plays a critical role in maintaining the stemness and expansion of cancer cells [49, 209]. To study therapeutic models in cancer research, 3D organoid models of ductal pancreatic cancers have provided a new spectrum of models of tumor progression by forming neoplasms that proceed to form invasive and metastatic carcinomas [210]. The organoid methodology is a useful system that can be used to identify the characteristics of malignancy, and the creation of complete tissues or neoplastic cancer organoids in vitro might provide better models of cancers in the future [35, 211–214].…”

Organoids – New Models for Host–Helminth Interactions

“…Part of this revolution has been in their use for a better understanding of host-pathogen interactions. Organoid models have been used to investigate viral, bacterial, and protozoan parasite infections [1,[3][4][5][6].…”

“…Currently, organoids are used as models of different pathologies, including infectious diseases caused by viruses, bacteria, and protozoans [3][4][5]. Viral infection studies with organoid systems have included: norovirus, rotavirus, enteric adenovirus, and coronavirus invasion of intestinal organoids [3][4][5][6]; herpes simplex virus 1 [23] and cytomegalovirus [24] infection of cerebral organoids; Zika virus infection of cerebral [4,5] and human testicular organoids [25]; human airway organoids to model pathology and assess infectivity of emerging influenza [26], parainfluenza [27] and respiratory syncytial viruses [28]; BK virus infection in human kidney tubuloids [29]; and human liver organoids to study infection with hepatitis B and its related tumorigenesis [30].…”

“…Organoid models of bacterial pathogenesis include enterohaemorrhagic, enteroaggregative, and enteropathogenic Escherichia coli, Vibrio cholerae, Salmonella, Clostridium difficile, and Shigella infecting intestinal organoids of mouse, bovine, porcine, and human origin [3][4][5][6]31], as well as Helicobacter pylori colonizing gastric (stomach) organoids [4][5][6]. In addition, the involvement of bacteria in adenocarcinoma formation in gallbladders has been studied using murine gallbladder organoids infected with Salmonella [4,5]. Infection with the uropathogen Enterococcus faecalis has been studied in human urothelial organoids [32].…”

“…Organoids can be utilized in their 3D conformation, when grown embedded in an ECM, or as 2D monolayers grown over plasticware or permeable supports/transwells coated with ECM [3][4][5][6]54,55]. The 2D models require numerous 3D organoids to be dissociated into single cells.…”