2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeriamonocytogenes infection in mice

Exposure to different forms of psychological and physiological stress can e licit a host stress response, which alters normal parameters of neuroendocr ine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administere d to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial path ogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial gr owth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infecti on demonstrated an enhanced resistance to the listeria challenge. The enhan ced bacterial clearance in vivo could not be explained by 2-DG exerting a t oxic effect on the listeria, based on the results of two experiments. First , 2-DG did not inhibit listeria replication in trypticase soy broth. Second , replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2- DG, which correlated with the increased resistance to L. monocytogenes. The se results support the contention that the host response to 2-DG-induced me tabolic stress can influence the capacity of the immune system to resist in fection by certain classes of microbial pathogens. (C) 1998 Elsevier Scienc e Inc.