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.
Bibliographical noteFunding Information:
Received 11 February 2008; accepted 26 March 2008; electronically published 15 July 2008. Potential conflicts of interest: none reported. Financial support: National Institutes of Health (grants DA023543-01 to T.W.M. and T32 DA007097-26A1 to T.W.M.). Reprints or correspondence: Dr. Phillip K. Peterson, Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota, 3–216 6th Street SE, Minneapolis, MN 55455 (email@example.com).