Fig. 1.

S1P₁R agonism blunts innate cellular and cytokine responses independently of TLR3 or -7 signaling. TLR3^−/− (A) or TLR7^−/− (B) mice were infected with 1 × 10⁴ PFU WSN influenza virus and either vehicle (water) or CYM5442 (2 mg/kg) were administered intratracheally to mice. Proinflammatory cytokines and chemokines were measured 48 h postinfection in BALF by ELISA. Total numbers of activate macrophages/monocytes and NK cells (C and E) were quantified from collagenase-digested lungs at 48 h postinfluenza virus infection. (D and F) Total numbers of neutrophils isolated from collagenase-digested lungs. *P < 0.05, **P < 0.01, ***P < 0.005. Results are representative of two to three independent experiments and five mice per group.