PD-L1 blockade overrides Salmonella typhimurium-mediated diabetes prevention in NOD mice: no role for Tregs.

Increasingly, evidence suggests that there is a strong environmental component to the development of the autoimmune disease type 1 diabetes. Our previous data showed that NOD mice are protected from developing diabetes after infection with Salmonella typhimurium and there is some evidence that changes within the DC compartment play a crucial role in this protective effect. This paper further characterises this Salmonella-modulated protective phenotype. We find that, contrary to other infection-mediated models of type 1 diabetes protection, there was no expansion of Foxp3(+) Tregs. Furthermore, transcriptome analysis of DCs identified a distinct Salmonella-induced signature in which the inhibitory receptor PD-L1 was up-regulated. This was confirmed by flow cytometry. In vivo blockade of the PD1/PD-L1 interaction was found to ablate the protective function of Salmonella infection. These data provide evidence for a novel regulatory DC phenotype proficient at controlling autoreactive T cells for an extended duration in the NOD mouse model of diabetes.