Figure 6.

Mitochondrial complex II contributes to macrophage bactericidal capacity. (a-c) OCR upon sequential treatment with oligomycin (olig.), CCCP, and rotenone+antimycin (Rot.+Ant.) (a), SRC (b), and ECAR (c) in BMDMs stimulated for 2h with E. coli ± NPA. (d) Survival of WT mice infected with 1x10⁹ S. enterica Typhimurium by gavage and treated or not with 50mg/kg NPA. (e, f) Splenic bacterial burdens at 72h (e) and cytokine serum levels at 2h (f) after intra-peritoneal injection of 1 x 10⁸ (e) or 1 x 10⁹ (f) of E. coli (f) into WT mice treated or not NPA. (g, h) Intracellular CFU (g) and anti-GFP immunoblot of SDS-solubilized extracts (h) from WT BMDMs treated or not with NPA and infected with E. coli (g) or GFP-expressing E. coli (h) at MOI = 5 for the indicated times. (i) CFU of 1x10⁵ E. coli incubated 3h with itaconic acid, dimethyl (DM)-succinate or DM-fumarate. (j) S. enterica Typhimurium growth in presence of 10mM of the indicated reagent. NS, not significant; *P < 0.05; **P < 0.01; ***P < 0.001 (Student’s t-test (b, c, e-g, i, j) or Log-rank (Mantel-Cox) test (d)). Data are from three independent experiments performed in two to five technical replicates (b-g, i, j). Data (mean and s.e.m. in (b,c, e-g, i, j); mean and s.d. in (a)) are from two (d, f, g) and three (b, c, e, i, j) independent experiments performed in three (j) or five (b, c) technical replicates or with two to five mice per group (e, f), one representative of at three independent experiments with similar results (a, h).