LRRK2 kinase activity is required for host defense against S. Typhimurium infection. (a) WT mice were intraperitoneally injected with LRRK2 inhibitor GSK2578215A (100 mg/kg) 1 h before S. Typhimurium infection. Peritoneal cells were collected for detecting LRRK2 phosphorylation 6 h after infection. (b) ELISA analysis of IL-1β levels in PCF and sera of WT and GSK2578215A-pretreated mice 6 h after S. Typhimurium infection. (c) Absolute number of total peritoneal cells and neutrophils (CD11b⁺ Ly6G⁺) from PCF of WT and GSK2578215A-pretreated mice 6 h after S. Typhimurium infection. (d) Bacterial burden in blood, PCF, and spleens of WT and GSK2578215A-pretreated mice 24 h after S. Typhimurium infection. (e) Peritoneal macrophages from littermate control (WT) and LRRK2 G2019S transgenic mice were infected with S. Typhimurium at an MOI of 50 for 1 h. Cells were dissolved with Triton X-100–containing buffer followed by cross-linkage of insoluble fractions with DSS to capture ASC oligomers. Immunoblots of those insoluble fractions (Insoluble + DSS) and soluble fractions were detected with an antibody to ASC. (f) LPS-primed peritoneal macrophages from WT and LRRK2 G2019S transgenic mice were infected with S. Typhimurium at an MOI of 100 for 2 h. Cell lysates and culture supernatants (Sup) were collected and blotted with the indicated antibodies. (g) ELISA analysis of IL-1β levels in PCF and sera from littermate control WT and LRRK2 G2019S transgenic mice 6 h after S. Typhimurium infection. (h) Absolute number of total peritoneal cells and neutrophils (CD11b⁺ Ly6G⁺) from PCF of littermate control and LRRK2 G2019S transgenic mice 6 h after S. Typhimurium infection. (i) Bacterial burden in blood, PCF, and spleens of littermate control and LRRK2 G2019S transgenic mice 12 h after S. Typhimurium infection. Data are shown as means ± SEM; *, P < 0.05; **, P < 0.01; ***, P < 0.001; determined by Student’s t test. All data are representative of three independent experiments, and n = 5 mice/group for each experiment.