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.

Figure 1

Illustration of the “chain of infection” model. Infection results from the interaction between the host, microbe and the environment. Six elements together constitute the chain of infection starting from pathogen, reservoir, portal of exit, means of transmission, portal of entry and ends with the infection of a new host. Organoids can be used to study the various links of the “chain of infection” model and help in the prevention and treatment of infectious diseases.

Figure 2

Methods of studying host–microbe interactions. Organoids can be microinjected with the microbe using a fine capillary microinjector. In this case the microbe is in direct contact with the apical side of epithelial cells. Organoids can also be sheared into smaller pieces, mixed with pathogen and re-plated with Matrigel/BME. Alternatively, 3D organoids can be dissociated into single cells by enzymatic treatment and grown as 2D monolayer cultures. Microbes are then introduced into the media.