Metabolic thresholds influence Mtb pathogenesis.

<p>A. In parallel sets, THP-1 cells and primary human PBMC-derived macrophages (HuMφ were infected with the indicated strains, and cultured either in complete RPMI (Utr), or in media supplemented with 5TG (10 mM). Bacterial load was then determined as CFU values at 72 hr p-i (n = 3, mean ±SD). B, C. Groups of 6–8 mice were either left untreated (Ctrl), or rendered hypoglycemic through insulin administration (Ins, 60 IU/kg/day), or were treated with Streptozotocin (180 mg/kg) to induce diabetes (STZ). Panel ‘B’ gives the blood sugar levels (mean ±S.D.) in the mice after the respective treatments. These mice were infected with H37Rv and lung CFU values determined at the times indicated (C). Values are the mean ±S.D. (significance *p<0.05, **p<0.01). D. Lung CFUs in H37Rv-infected diabetic mice that were either left untreated (Ctr), or treated with 12 mg/Kg/day of UK5099 (8 mice/group, mean ±SD, significance *p<0.05). E. The relative proportion of cells undergoing either apoptosis (brown bars) or necrosis (blue bars) in THP-1 cells infected with the individual virMtb strains is shown. Result for a parallel set of JAL2287-infected cells that were maintained in medium supplemented with 5TG is also given. Analysis was at 72 hr p-i (n = 3, mean ±SD). 1: JAL2261; 2: H37Rv; 3: BND433; 4: JAL2287; 5: JAL2287 + 5TG. F–G. Lung CFUs in mice after 30 days of infection with the indicated Mtb strains (F). Data are mean ± S.D. of 8 mice/group. Panel ‘G’ gives the total number of granulomas seen in three lung sections from the mice in each group. *p<0.05, **p<0.01.