Mitofusin-2 boosts innate immunity through the maintenance of aerobic glycolysis and activation of xenophagy in mice

摘要

a–d Intracellular survival assay after Mtb (MOI 3; n = 6) (a), BCG (MOI 3; n = 6) (b), M. abscessus (M.abs)-smooth (MOI 1 and 3; n = 4) (c), and LM (MOI 1 and 5; n = 4) (d) infection assessed in Mfn2 WT and Mfn2 CKO BMDMs after indicated time duration. e–g In vivo bacterial load in lung tissues from Mtb (e; n = 6, 5 × 104 CFU), BCG (f; 2 × 106 CFU, n = 3 and 1 × 107 CFU, n = 5) at 7 days post infection (dpi) or M.abs (g; smooth n = 5, 2 × 106 CFU and rough n = 4, 1 × 107 CFU)-infected Mfn2 WT and Mfn2 CKO mice. h H&E staining of the BCG-infected lung tissue from Mfn2 WT and Mfn2 CKO mice. Representative images are shown. Scale bars, 100 μm. i, j Survival rate of Mfn2 WT and Mfn2 CKO mice infected with LM i.v. (WT n = 6, CKO n = 5) (i) and i.p. (n = 7) (j) monitored for indicated time. k In vivo bacterial load in liver and spleen from Mfn2 WT and Mfn2 CKO mice infected with LM (i.p.) for 72 h (n = 5). l Daily change in body weight of Mfn2 WT and Mfn2 CKO mice after LM infection. Loss of body weight is calculated subtracting the body weight of each day to that of day 0 (n = 7). Mean ± SEM are shown (a–g, k, l). Two-tailed Student’s t tests (a–g, k, l) and log-rank (Mantel–Cox) test (i, j) were used to measure the significance.