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.
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-
) 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-
-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-
or a key member of the
IFN signaling pathway, interferon regulatory factor 1. Thus while
IFN-
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.
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