Conclusion
Together, our model shows how T. gondii infection shapes the retinal cytokine network and barrier function, and demonstrates the role of type I and type III interferons in these processes.
Discussion
Here, we show that stimulation with type I and III interferons did not limit parasite proliferation in retinal cells we tested. However, IFN-β and IFN-γ strongly induced inflammatory or cell-attracting cytokine production, whereas IFN-λ1 showed less inflammatory activity. Concomitant T. gondii infection influenced these cytokine patterns, distinctly depending on the parasite strain. Interestingly, all these cells could be stimulated to produce IFN-λ1. Using an in vitro oBRB model based on RPE cells, we observed that interferon stimulation strengthened membrane localization of the tight junction protein ZO-1 and enhanced their barrier function, in a STAT1-independent manner. Conclusion: Together, our model shows how T. gondii infection shapes the retinal cytokine network and barrier function, and demonstrates the role of type I and type III interferons in these processes.
Methods
As a first approach, we studied the initial cytokine network in vitro in four human cell lines: Retinal pigmented epithelial (RPE), microglial, astrocytic and Müller cells. Furthermore, we looked at the consequences of retinal infection on the integrity of the outer blood-retina barrier (oBRB). We particularly focused on the roles of type I and type III interferons, (IFN-β and IFN-λ). Especially IFN-λ is known for its significant role in barrier defense. However, its effect on the retinal barrier or T. gondii infection remains unexplored, unlike IFN-γ, which has been extensively studied in this context.