TRAIL limits excessive host immune responses in bacterial meningitis
J. Clin. Invest. Olaf Hoffmann, et al. 117:2004 doi:10.1172/JCI30356 [Go to this article.]

Figure 4
rTRAIL modulates inflammation and apoptosis in the hippocampus of wild-type and TRAIL^–/– mice with meningitis. (A–C) FACS analysis of murine peripheral blood demonstrates the presence of TRAIL-R2 on Gr-1–positive leukocytes. (A) Gr-1 staining and isotype control staining for TRAIL-R2. PE, phycoerthrin. (B) Double staining for Gr-1 and TRAIL-R2. (C) Histogram plot of TRAIL-R2 expression in the gated Gr-1^high population. Isotype control (gray curve); TRAIL-R2 (black curve). (D–F) Effects of treatment with rTRAIL in experimental meningitis. (D) In TRAIL^–/– mice, a dose-dependent reduction of pleocytosis was observed 24 hours after intrathecal administration of 0.1–1 μg rTRAIL and PCW. In wild-type mice, rTRAIL had no effect. (E) At 12 hours after meningitis induction, coapplication of 1 μg rTRAIL with PCW reduced the levels of pleocytosis in wild-type mice and TRAIL^–/– mice. (F) rTRAIL reduced apoptosis in the dentate gyrus at 24 hours after meningitis induction in wild-type and TRAIL^–/– mice. (G) Parenteral administration of an antibody against CD18 significantly reduced the recruitment of leukocytes across the blood-brain barrier in wild-type mice. (H) CD18 inhibition also diminished the number of TUNEL-positive cells in the dentate gyrus at 24 hours after meningitis induction in wild-type mice. (D–H) *P < 0.05; **P < 0.01, Student’s t test or Mann-Whitney U test as appropriate. (I) In TRAIL^–/– mice, depletion of granulocytes with an antibody against Ly6G reduced the number of TUNEL-positive cells in the dentate gyrus at 24 hours after meningitis induction. **P < 0.01, Student’s t test. Intrathecal treatment with 1 μg rTRAIL diminished apoptosis in the dentate gyrus of nondepleted mice at 24 hours after meningitis induction (P < 0.01, Student’s t test), but no additional effect of rTRAIL was present in granulocyte-depleted mice. P = NS, 2-way ANOVA. DG, dentate gyrus.