Es. Miller et al., 2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeriamonocytogenes infection in mice, PHYSL BEHAV, 65(3), 1998, pp. 535-543
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.