Immune Netw.  2009 Apr;9(2):46-52. 10.4110/in.2009.9.2.46.

The Role of Nitric Oxide in Mycobacterial Infections

• Yang CS
• Yuk JM
• Jo EK

• KMID: 1474594
• DOI: http://doi.org/10.4110/in.2009.9.2.46

Abstract

Although tuberculosis poses a significant health threat to the global population, it is a challenge to develop new and effective therapeutic strategies. Nitric oxide (NO) and inducible NO synthase (iNOS) are important in innate immune responses to various intracellular bacterial infections, including mycobacterial infections. It is generally recognized that reactive nitrogen intermediates play an effective role in host defense mechanisms against tuberculosis. In a murine model of tuberculosis, NO plays a crucial role in antimycobacterial activity; however, it is controversial whether NO is critically involved in host defense against Mycobacterium tuberculosis in humans. Here, we review the roles of NO in host defense against murine and human tuberculosis. We also discuss the specific roles of NO in the central nervous system and lung epithelial cells during mycobacterial infection. A greater understanding of these defense mechanisms in human tuberculosis will aid in the development of new strategies for the treatment of disease.

Keyword

nitric oxide; mycobacteria; macrophages; host defense

MeSH Terms

Bacterial Infections
Central Nervous System
Defense Mechanisms
Epithelial Cells
Humans
Immunity, Innate
Lung
Macrophages
Mycobacterium tuberculosis
Nitric Oxide
Nitric Oxide Synthase
Nitrogen
Tuberculosis
Nitric Oxide
Nitric Oxide Synthase
Nitrogen

Figure

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  Figure 1 Yang et al. Synthesis, regulation, and antimycobacterial function of NO in mycobacterial infection. Activated inducible nitric oxide synthase (iNOS) produces Nω-OH-L-arginine from L-arginine, and then Nω-OH-L-arginine is transduced to form NO and L-citruline. Synthesis of NO and reactive nitrogen oxides (RNI) are positively regulated by Th1 cytokines, whereas they are negatively regulated by Th2 cytokines. Produced NO and RNIs, which combined with NO and O2-, can directly kill intracellular MTB in the infected cells (including macrophages, epithelial and glial cells), although the action of NO is dependent on the species and specific cell types.

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