Epithelial Cell Coculture Models for Studying Infectious Diseases: Benefits and Limitations
Figure 1
Examples of coculture models for the study of infection. A. Monolayer cocultures typically incorporate epithelial cells and another adherent cell type(s) and these detect microbes (I) and signal via juxtacrine mechanisms (black arrow) to cells in the monolayer to induce synthesis of immune factors and cytokines. Microbes that bind or invade epithelial cells may induce signals from the partner cell types in the monolayer, which can release inflammatory molecules (II) such as nitric oxide (NO) or reactive oxygen species (ROS). In models that utilize viable microbes overgrowth can lead to cytotoxicity of host cells in the monolayer (III) and may limit the study. B. Suspension cocultures often utilize phagocytes that ingest microbes and signal other cells to proliferate (I). Suspension coculture models sometimes use dynamic conditions such as rolling and may incorporate immature or mature versions of cell lineages such as monocytes or macrophages. Intercellular signalling can occur via juxtacrine pathways (black arrow) where receptors are ligated and can lead to the induction of inflammatory molecules (II). Alternatively, cells may respond to immune factors as co-stimulatory molecules that are required for optimal responses to microbes (III) such as production of regulatory factors. C. Mixed cocultures typically utilize adherent monolayers in combination with a suspension cell type(s), which can respond to co-stimulation by differentiation (I). Microbe binding to suspension cells may lead to cytokine/immune factor signalling of the adherent cells to induce the secretion of inflammatory molecules by the monolayer (II). Phagocytes present in the coculture may ingest microbes and signal to the adherent cells via an unknown receptor mechanism to promote juxtacrine signalling between cells (black arrow) as a means to trigger downstream regulatory factors (III). Microbe binding to adherent cells may stimulate paracrine signalling to suspension cells, recruiting them towards the monolayer (IV).
