Defective host defense of PGRN-deficient mice. (A) Enhanced MCP-1 levels in PGRN-deficient mice in response to infection. WT and PGRN-deficient mice (n = 10 per group) were infected intravenously with 3 × 10³ L. monocytogenes. MCP-1 levels in serum and spleen homogenates were determined 24 h after infection by ELISA. Hippocampal expression of MCP-1 was determined by real-time RT-PCR 5 d after infection and expressed as relative levels after normalization with GAPDH mRNA. Results are means ± SEM. *, P < 0.05 using the Student’s t test. ND, nondetectable. (B) Decreased monocyte recruitment to infected spleens of PGRN-deficient mice. Cells from naive or infected spleen (24 h after infection) were tested for the expression of CD11b and Ly6C (for monocyte population). Numbers in dot plots indicate the percentage of Ly6C^hiCD11b⁺ cells. Dot plots are of individual mice; bar graphs represent the mean of five mice per group. Experiments were repeated three times with similar results. *, P < 0.05 using the Student’s t test. (C) Inability to rapidly resolve bacterial infection by PGRN-deficient mice. WT and PGRN-deficient (KO) mice were infected intravenously with 5 × 10³ L. monocytogenes. Bacterial burdens in the spleen, liver, and brain were measured as CFUs at the times indicated (n = 5 per genotype for days 3 and 5 after infection; n = 10 per genotype for day 7 after infection). Results are means ± SEM from one out of three similar experiments. (D) Exaggerated tissue inflammation in PGRN-deficient mice, as assessed by hematoxylin and eosin staining at day 3 (liver) or 5 (brain) after intravenous infection with 5 × 10³ L. monocytogenes. Results are means ± SEM from one out of three similar experiments. Bars, 200 µm.