Toll-like receptor 2 is protective of ischemia-reperfusion-mediated small-bowel injury in a murine model

Objective. In a murine model of intestinal injury, we hypothesized that Toll-like receptor 2 (TLR2), a recognition molecule for commensal bacteria, plays an important role in the development of mucosal immunity and is protective against ischemia/reperfusion injury via the modulation of both innate and acquired immunity. Design: Interventional laboratory study. Setting: Academic medical research center. Subjects. Four-week-old C57BL6 wild-type (n = 12) and C57BL6 TLR2-deficient mice (TLR2(-/-)) (n = 12). Interventions: Twenty-four mice underwent laparotomy only or laparotomy plus superior mesenteric artery occlusion (n 6/group) for 60 mins, followed by 90 mins of recovery. Measurements and Main Results: Mid-jejunal sections were taken for histopathology and messenger RNA expression (reverse transcriptase-polymerase chain reaction, normalized to 18s and laparotomy-only controls). Intestinal injury was scored from 0 (no injury) to 4 (transmural necrosis). Statistical analyses were performed using Mann-Whitney U test and Student's Mest (p < .05 significant). TLR2(-/-) mice had elevated intestinal injury scores (mean +/- SEm) after ischemia/reperfusion vs. wild-type (2.17 +/- 0.40 vs. 0.67 +/- 0.33, p < .05). Intestinal cytokine messenger RNA (mean fold change +/- SEM) of interferon-gamma (0.29 +/- 0.12 vs. 3313 +/- 1710), interieukin-4 (0.25 +/- 0.13 vs. 2.70 +/- 1.08), and interleukin-6 (250.63 +/- 69.60 vs. 320,300 +/- 215,964) in TLR2(-/-) was significantly decreased (p < .05) after ischemia/reperfusion vs. wild-type. Tumor necrosis factor-et messenger RNA levels were unchanged. Conclusions: TLR2(-/-) mice have a dysregulated mucosal innate immune response and fail to mount a protective response after ischemia-reperfusion compared with wild-type mice. This murine model of intestinal injury may correlate with the early postnatal course of premature infants who may have decreased TLR2 expression and/or decreased luminal commensal bacteria secondary to antibiotic therapy, thus decreasing TLR2-mediated signaling.