*2.3. Cecal Ligation and Perforation*

After four weeks of AAV1 injection, the mice were subjected to cecal ligation and perforation or sham surgery. The cecal ligation and puncture (CLP) model, which closely mimics the clinical features of human sepsis [31], was performed to induce polymicrobial sepsis as described previously [30,33] with minor modifications. Briefly, the mice were first anesthetized with isoflurane (~3%; Piramal Critical Care). A midline abdominal incision (~2 cm) was then performed. The cecum was carefully ligated at ~1 cm from its distal portion. The ligated cecum was perforated by a through-and-through puncture performed with 251/<sup>2</sup> gauge needle in a sterile environment. Next, the ligated cecum was gently compressed to extrude a small amount of the cecal contents through the punctured holes. The cecum was then replaced in the abdominal cavity. The peritoneum was then closed in two separate layers using 3–0 absorbable polyfilament interrupted sutures. The skin was finally closed with a surgical staple (9 mm AutoClip® System, Fine Scientific tools, North Vancouver, BC, Canada). All of the animals received subcutaneous injections of buprenorphine (0.05 to 0.2 mg/kg in 1 mL of 0.9% saline) immediately after surgery. To minimize pain, buprenorphine was administered every 12 h (0.05 mg/kg in ~100 μL of 0.9% saline). The sham-operated mice were subjected to identical procedures with the exception of the cecum ligation and puncture. All of the animals were closely monitored for signs of excessive pain or distress, such as lack of movement, agonal breathing or excessive body loss (20%), by investigators and by the vivarium staff from the IR-MUHC. Any mouse reaching endpoint criteria was immediately euthanized.
