TRAIL limits excessive host immune responses in bacterial meningitis
J. Clin. Invest. Olaf Hoffmann, et al. 117:2004 doi:10.1172/JCI30356 [
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Figure 3Apoptosis in the hippocampus and clinical impairment are augmented in TRAIL
–/– mice with meningitis.
(
A) Twenty-four hours after meningitis induction, there is an increase in the number of TUNEL-positive apoptotic cells/mm
2 of the dentate gyrus in TRAIL
–/– mice and wild-type mice compared with that in PBS-treated controls. *
P < 0.05; **
P < 0.01, 1-way ANOVA with Student-Neuman-Keuls post hoc analysis. Meningitis caused a much stronger increase of apoptotic cell death in TRAIL
–/– mice than in wild-type mice compared with controls.
##P < 0.01, Student’s
t test. Examples of TUNEL-stained cells are shown in Supplemental Figure 2. (
B) Correlation of the number of TUNEL-positive cells/mm
2 in the dentate gyrus with the concentration of CSF leukocytes at 24 hours after meningitis induction. Multiple regression analysis identified the leukocyte count as a stronger predictor of damage than the genotype (T
leukocytes = 7.2; T
genotype = 2.0). (
C and
D) Motor and coordination assessment with the tightrope test at 18 hours (
C) and 24 hours (
D) after meningitis induction. Clinical impairment is more pronounced in TRAIL
–/– mice compared with wild-type mice. **
P < 0.01, log rank test. All control mice were able to hold on to the rope for at least 30 seconds.
