PD-L1 expression in tissues of cats with naturally occurring feline infectious peritonitis

Among feline coronaviruses (FCoVs), feline enteric coronavirus (FECV) is a ubiquitous enteric pathogen in feline populations and responsible for asymptomatic to mild enteric disease. However, in a small number of cats, viral mutations within the host combined with impaired host immune responses may lead to feline infectious peritonitis (FIP), a fatal, systemic infection. Programmed death-1 (PD-1) is a major immune-checkpoint protein expressed on activated T cells, and its engagement by the ligands PD-L1 and PD-L2 on target cells leads to suppression of T-cell activity. Previously, we found that infection with FIPV, but not FECV, up-regulated the expression of PD-L1 in feline cell lines, which attenuated T-cell activities. We also demonstrated that feline interferons (IFNs), particularly IFN-γ, are potent inducers of PD-L1 in cells. In this study, we assess the expression of PD-L1 in association with FIPV in the tissues of four cats with naturally occurring FIP using histopathology, real-time RT-qPCR, and confocal microscopy. By confocal microscopy, we found that numerous cells co-localized with FCoV and PD-L1 in various tissues of all animals, with about 50% of FCoV-positive cells also stained with PD-L1. Interestingly, about 10% of PD-L1 positive cells were also positive for FCoV, which is likely due to severe inflammation and cytokines such as IFN-γ. These findings support a tissue-level association between PD-L1 expression and FCoV infection in some tissues from cats with FIP, while also indicating substantial variation among tissues and animals.