Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens.
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.
Nathan
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Department of Microbiology and Immunology and Department of Medicine, Weill Cornell Medical College and Program in Immunology, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10021, USA. cnathan@med.cornell.edu
Shiloh
M U
MU
D000818:Animals; D006801:Humans; D008322:Mammals / Q000276:immunology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism*; D017382:Reactive Oxygen Species
D017382:Reactive Oxygen Species; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; D009584:Nitrogen