Susceptibility of Card9^−/− mice to tuberculosis is caused by increased granulopoiesis and accelerated neutrophil recruitment to inflamed lungs. (A) Neutrophil accumulation in lungs during TB in Card9^−/− mice and (B) expression of the costimulatory molecule CD86 on surface of lung DCs and macrophages. (C and D) Analysis of cytokine and chemokine concentrations in lung homogenates and sera revealed that Card9^−/− mice developed systemic inflammatory responses with increased local proinflammatory cytokines and high levels of soluble mediators of granulocyte development and chemotaxis at day 14 p.i. (C) and day 24 p.i. (D). (E) Increased serum levels of granulocyte MPO in Card9^−/− mice. (F) Up-regulation of PMN-related genes in lung of infected mice 14 d p.i. (G) Card9^−/− mice presented multiple clusters of MPO⁺ granulocytes within large inflammatory lung infiltrates. Bar, 100 µm. Data are representative of two independent experiments (n = 5). Two-way ANOVA and Bonferroni method were applied for statistical analyses. **, P < 0.01; ***, P < 0.001.