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Infection and Immunity, December 2000, p. 6879-6882, Vol. 68, No. 12
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Expression of the Nitric Oxide Synthase 2 Gene Is Not Essential for Early Control of Mycobacterium tuberculosis in the Murine Lung

Andrea M. Cooper,1,* John E. Pearl,1 Jason V. Brooks,1 Stefan Ehlers,2 and Ian M. Orme1

Mycobacterial Research Laboratories, Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523,1 and Division of Molecular Infection Biology, Research Center Borstel, Center for Medicine and Biosciences, D-23845 Borstel, Germany2

Received 24 July 2000/Returned for modification 1 September 2000/Accepted 21 September 2000

The interleukin-12 and gamma interferon (IFN-gamma ) pathway of macrophage activation plays a pivotal role in controlling tuberculosis. In the murine model, the generation of supplementary nitric oxide by the induction of the nitric oxide synthase 2 (NOS2) gene product is considered the principal antimicrobial mechanism of IFN-gamma -activated macrophages. Using a low-dose aerosol-mediated infection model in the mouse, we have investigated the role of nitric oxide in controlling Mycobacterium tuberculosis in the lung. In contrast to the consequences of a systemic infection, a low dose of bacteria introduced directly into the lungs of mice lacking the NOS2 gene is controlled almost as well as in intact animals. This is in contrast to the rapid progression of disease in mice lacking IFN-gamma or a key member of the IFN signaling pathway, interferon regulatory factor 1. Thus while IFN-gamma is pivotal in early control of bacterial growth in the lung, this control does not completely depend upon the expression of the NOS2 gene. The absence of inducible nitric oxide in the lung does, however, result in increased polymorphonuclear cell involvement and eventual necrosis in the pulmonary granulomas of the infected mice lacking the NOS2 gene.

* Corresponding author. Mailing address: Department of Microbiology, Colorado State University, 200 West Lake, Fort Collins, CO 80523. Phone: (970) 491-2833. Fax: (970) 491-1815. E-mail: acooper{at}cvmbs.colostate.edu.

Infection and Immunity, December 2000, p. 6879-6882, Vol. 68, No. 12
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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