Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens
Carl Nathan,Michael U. Shiloh +1 more
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TLDR
This review summarizes recent evidence from knock-out mice on the role of reactive oxygen intermediates and reactive nitrogen intermediates (RNI) in mammalian immunity and identifies candidates for RNI-resistance genes in Mycobacterium tuberculosis and other 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.read more
Citations
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Nitric oxide and the immune response
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Myeloperoxidase: friend and foe
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Dirk Schnappinger,Sabine Ehrt,Martin I. Voskuil,Yang Liu,Joseph A. Mangan,Irene M. Monahan,Gregory Dolganov,Brad Efron,Philip D. Butcher,Carl Nathan,Gary K. Schoolnik +10 more
TL;DR: The microbial transcriptome served as a bioprobe of the MTB phagosomal environment, showing it to be nitrosative, oxidative, functionally hypoxic, carbohydrate poor, and capable of perturbing the pathogen's cell envelope.
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References
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Nitric oxide as a secretory product of mammalian cells.
TL;DR: How different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule is reviewed.
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Nitric oxide and macrophage function
TL;DR: Although the high-output NO pathway probably evolved to protect the host from infection, suppressive effects on lymphocyte proliferation and damage to other normal host cells confer upon NOS2 the same protective/destructive duality inherent in every other major component of the immune response.
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TL;DR: Peroxynitrite anion was a less effective thiol-oxidizing agent than its anion, with oxidation presumably mediated by the decomposition products, hydroxyl radical and nitrogen dioxide.
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An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection.
JoAnne L. Flynn,John Chan,Karla J. Triebold,Dyana K. Dalton,Timothy A. Stewart,Barry R. Bloom +5 more
TL;DR: Gko mice have been developed which fail to produce IFN-gamma (gko), because of a targeted disruption of the gene for IFNs, and succumb to a rapid and fatal course of tuberculosis that could be delayed, but not prevented, by treatment with exogenous recombinant IFN.
Journal ArticleDOI
Nitric oxide functions as a signal in plant disease resistance
TL;DR: It is shown that nitric oxide potentiates the induction of hypersensitive cell death in soybean cells by reactive oxygen intermediates and functions independently of such intermediates to induce genes for the synthesis of protective natural products.
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