Abstract
ABSTRACTThe interleukin-12 and gamma interferon (IFN-γ) 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-γ-activated macrophages. Using a low-dose aerosol-mediated infection model in the mouse, we have investigated the role of nitric oxide in controllingMycobacterium tuberculosisin 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-γ or a key member of the IFN signaling pathway, interferon regulatory factor 1. Thus while IFN-γ 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.
References
30
Referenced
112
10.1016/S0962-8479(97)90004-6
-
Bean A. G. D. Roach D. R. Briscoe H. France M. P. Korner H. Sedgewick J. D. Britton W. J. Structural deficiencies in granuloma formation in TNF gene-targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin.J. Immunol.162199935043511
(
10.4049/jimmunol.162.6.3504
) / J. Immunol. / Structural deficiencies in granuloma formation in TNF gene-targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin by Bean A. G. D. (1999) 10.1046/j.1365-3083.1999.00522.x
10.1128/iai.63.2.736-740.1995
10.1084/jem.175.4.1111
10.1016/S0962-8479(97)90017-4
10.1084/jem.178.6.2243
10.1128/IAI.68.3.1231-1234.2000
10.1084/jem.192.1.117
-
Doherty T. M. Sher A. Defects in cell-mediated immunity affect chronic, but not innate, resistance of mice to Mycobacterium avium infection.J. Immunol.158199748224831
(
10.4049/jimmunol.158.10.4822
) / J. Immunol. / Defects in cell-mediated immunity affect chronic, but not innate, resistance of mice to Mycobacterium avium infection by Doherty T. M. (1997) 10.1165/ajrcmb.23.2.4063
10.1046/j.1365-2567.1999.00875.x
-
Gomes M. S. Florido M. Pais T. F. Appelberg R. Improved clearance of Mycobacterium avium upon disruption of the inducible nitric oxide synthase gene.J. Immunol.162199967346739
(
10.4049/jimmunol.162.11.6734
) / J. Immunol. / Improved clearance of Mycobacterium avium upon disruption of the inducible nitric oxide synthase gene by Gomes M. S. (1999) 10.1126/science.7510419
10.1073/pnas.92.23.10688
10.1073/pnas.94.10.5243
10.1128/IAI.67.8.3864-3871.1999
10.1016/S0092-8674(05)80086-8
10.1126/science.8009221
10.1128/IAI.67.7.3221-3226.1999
10.1016/S0966-842X(98)01209-8
10.1016/S0167-5699(98)01438-8
-
Orme I. M. Miller E. S. Roberts A. D. Furney S. K. Griffin J. P. Dobos K. M. Chi D. Rivoire B. Brennan P. J. T lymphocytes mediating protection and cellular cytolysis during the course of Mycobacterium tuberculosis infection. Evidence for different kinetics and recognition of a wide spectrum of protein antigens.J. Immunol.1481992189196
(
10.4049/jimmunol.148.1.189
) / J. Immunol. / T lymphocytes mediating protection and cellular cytolysis during the course of Mycobacterium tuberculosis infection. Evidence for different kinetics and recognition of a wide spectrum of protein antigens by Orme I. M. (1992) 10.1128/iai.65.4.1189-1195.1997
10.1016/S0962-8479(97)90016-2
10.1046/j.1365-2567.1999.00877.x
-
Schaible U. E. Sturgill-Koszycki S. Schlesinger P. H. Russell D. G. Cytokine activation leads to acidification and increases maturation of Mycobacterium avium-containing phagosomes in murine macrophages.J. Immunol.160199812901296
(
10.4049/jimmunol.160.3.1290
) / J. Immunol. / Cytokine activation leads to acidification and increases maturation of Mycobacterium avium-containing phagosomes in murine macrophages by Schaible U. E. (1998) 10.1084/jem.169.3.1011
10.1126/science.8303277
-
Xu S. Cooper A. M. Sturgill-Koszycki S. van Heyningen T. Chatterjee D. Orme I. Allen P. Russell D. G. Intracellular trafficking in Mycobacterium tuberculosis and Mycobacterium avium-infected macrophages.J. Immunol.153199425682578
(
10.4049/jimmunol.153.6.2568
) / J. Immunol. / Intracellular trafficking in Mycobacterium tuberculosis and Mycobacterium avium-infected macrophages by Xu S. (1994)
Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 27, 2002, 5:58 a.m.) |
Deposited | 2 years, 4 months ago (April 23, 2023, 11 a.m.) |
Indexed | 3 months, 2 weeks ago (May 14, 2025, 12:47 a.m.) |
Issued | 24 years, 9 months ago (Dec. 1, 2000) |
Published | 24 years, 9 months ago (Dec. 1, 2000) |
Published Print | 24 years, 9 months ago (Dec. 1, 2000) |
@article{Cooper_2000, title={Expression of the Nitric Oxide Synthase 2 Gene Is Not Essential for Early Control ofMycobacterium tuberculosisin the Murine Lung}, volume={68}, ISSN={1098-5522}, url={http://dx.doi.org/10.1128/iai.68.12.6879-6882.2000}, DOI={10.1128/iai.68.12.6879-6882.2000}, number={12}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Cooper, Andrea M. and Pearl, John E. and Brooks, Jason V. and Ehlers, Stefan and Orme, Ian M.}, editor={Clements, J. D.}, year={2000}, month=dec, pages={6879–6882} }