As an indispensable regulator of inflammation activation, S1PR1 plays a crucial role in immune cell trafficking and immune response (Rivera et al., 2008). When induced by SW8, S1PR1 expression was upregulated in the brain, lung, and spleen—by 5.51-, 2.29-, and 1.16-fold, respectively—but not in the bursa of Fabricius (0.17-fold). However, the expression level S1PR1 showed different tendencies when infected by ZH283. Unlike the expression level of TLR3 and TLR7, S1PR1 expression in the tested tissues after infection with ZH283 was lower than that in response to infection with SW8 (Figure 3C). Our data indicate that the engagement of PRRs and S1PR1 by the H5N6 influenza virus occurs in a tissue-dependent manner.