Open AccessTransient Loss of Resistance to Pulmonary Tuberculosis in p47phox−/−Mice
Author(s) -
Andrea M. Cooper,
Brahm H. Segal,
Arthur J. Frank,
Steven M. Holland,
Ian M. Orme
Publication year - 2000
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.68.3.1231-1234.2000
Subject(s) - superoxide , biology , microbiology and biotechnology , nadph oxidase , interferon gamma , immunology , mycobacterium tuberculosis , phagocyte , tuberculosis , cytokine , phagocytosis , reactive oxygen species , pathology , medicine , biochemistry , enzyme
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 controllingM. 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 withM. 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.