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Infection and Immunity, March 2000, p. 1231-1234, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Transient Loss of Resistance to Pulmonary Tuberculosis in p47phoxminus /minus Mice

Andrea M. Cooper,1,* Brahm H. Segal,2 Anthony A. Frank,3 Steven M. Holland,2 and Ian M. Orme1

Department of Microbiology1 and Department of Pathology,3 Colorado State University, Fort Collins, Colorado 80523, and Laboratory of Host Defense, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 208922

Received 19 October 1999/Returned for modification 17 November 1999/Accepted 30 November 1999

Mycobacterium tuberculosis is an important respiratory pathogen the growth of which is controlled primarily by cytokine-activated macrophages. One of the principal mediators of this control is nitric oxide; however, superoxide has recently been shown to be protective in systemic mycobacterial infections. To determine whether superoxide is important in controlling M. tuberculosis during primary pulmonary infection, mice lacking the cytosolic p47phox gene (which is essential for effective superoxide production by the NADPH oxidase) were infected aerogenically. The lack of superoxide during an aerosol infection with M. tuberculosis resulted in a significant increase in bacterial growth over the early period of infection. Once antigen-specific gamma interferon-producing lymphocytes were detected in the draining lymph nodes, however, bacterial growth in the lung stopped. One interesting consequence of the lack of superoxide was an increase in neutrophilic infiltrates within the granuloma. This may be a consequence of increased tissue damage due to more rapid bacterial growth or may reflect a role for superoxide in controlling inflammation.

* 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, March 2000, p. 1231-1234, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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