Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens
Abstract
This review summarizes recent evidence from knock-out mice on the role of reactive oxygen intermediates and reactive nitrogen intermediates (RNI) in mammalian immunity. Reflections on redundancy in immunity help explain an apparent paradox: the phagocyte oxidase and inducible nitric oxide synthase are each nonredundant, and yet also mutually redundant, in host defense. In combination, the contribution of these two enzymes appears to be greater than previously appreciated. The remainder of this review focuses on a relatively new field, the basis of microbial resistance to RNI. Experimental tuberculosis provides an important example of an extended, dynamic balance between host and pathogen in which RNI play a major role. In diseases such as tuberculosis, a molecular understanding of host–pathogen interactions requires characterization of the defenses used by microbes against RNI, analogous to our understanding of defenses against reactive oxygen intermediates. Genetic and biochemical approaches have identified candidates for RNI-resistance genes in Mycobacterium tuberculosis and other pathogens.
Footnotes
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↵ * To whom reprint requests should be addressed. E-mail: cnathan{at}med.cornell.edu.
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This paper was presented at the National Academy of Sciences colloquium “Virulence and Defense in Host–Pathogen Interactions: Common Features Between Plants and Animals,” held December 9–11, 1999, at the Arnold and Mabel Beckman Center in Irvine, CA.
- Abbreviations:
- NOS,
- nitric oxide synthase;
- phox,
- phagocyte oxidase;
- ROI,
- reactive oxygen intermediates;
- RNI,
- reactive nitrogen intermediates;
- SOD,
- superoxide dismutase;
- STM,
- signature-tagged transposon mutagenesis
- Copyright © 2000, The National Academy of Sciences
