Role of nitric oxide in defense of the central nervous system against Mycobacterium tuberculosis.
Murine models of tuberculous meningitis (TBM) have not reflected the severity of disease in humans. Based on reports that activated murine microglial cells, but not human microglial cells, express inducible nitric oxide synthase (iNOS), the objective of this study was to determine whether iNOS-knockout (iNOS(-/-)) mice would provide such a model. iNOS(-/-) mice infected with M. tuberculosis developed serious clinical manifestations and granulomatous lesions containing tubercle bacilli throughout the meninges, all of which were absent in wild-type mice. This study underscores the importance of nitric oxide in defense against TBM and suggests that iNOS(-/-) mice are an appropriate model for human TBM.
Olin
Michael R
MR
Veterinary Population Medicine, Veterinary Teaching Hospital, University of Minnesota, St. Paul, USA.
Armién
Aníbal G
AG
Cheeran
Maxim C-J
MC
Rock
R Bryan
RB
Molitor
Thomas W
TW
Peterson
Phillip K
PK
D000818:Animals; D002490:Central Nervous System / Q000201:enzymology* / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D009569:Nitric Oxide / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000172:deficiency* / Q000235:genetics; D014376:Tuberculosis / Q000235:genetics / Q000473:pathology*
D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II