The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 635K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Scharton-Kersten, T. M.
Right arrow Articles by Sher, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Scharton-Kersten, T. M.
Right arrow Articles by Sher, A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1997/4/1261/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 7, April 7, 1997 1261-1274

Article

Inducible Nitric Oxide Is Essential for Host Control of Persistent but Not Acute Infection with the Intracellular Pathogen Toxoplasma gondii

Tanya M. Scharton-Kersten*, George Yap*, Jeanne Magram{ddagger}, and Alan Sher*

From the * Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892; and {ddagger} Department of Inflammation and Autoimmune Diseases, Hoffmann-La Roche, Inc., Nutley, New Jersey, 07110

The induction by IFN-{gamma} of reactive nitrogen intermediates has been postulated as a major mechanism of host resistance to intracellular pathogens. To formally test this hypothesis in vivo, the course of Toxoplasma gondii infection was assessed in nitric oxide synthase (iNOS)–/– mice. As expected, macrophages from these animals displayed defective microbicidal activity against the parasite in vitro. Nevertheless, in contrast to IFN-{gamma}–/– or IL-12 p40–/– animals, iNOSdeficient mice survived acute infection and controlled parasite growth at the site of inoculation. This early resistance was ablated by neutralization of IFN-{gamma} or IL-12 in vivo and markedly diminished by depletion of neutrophils, demonstrating the existence of previously unappreciated NO independent mechanisms operating against the parasite during early infection. By 3-4 wk post infection, however, iNOS knockout mice did succumb to T. gondii. At that stage parasite expansion and pathology were evident in the central nervous system but not the periphery suggesting that the protective role of nitric oxide against this intracellular infection is tissue specific rather than systemic.

Address correspondence to Dr. Tanya Scharton-Kersten, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, Bldg. 4, Rm. 126, NIH, Bethesda, MD 20892.

1 Abbreviations used in this paper: CNS, central nervous system; iNOS, inducible nitric oxide synthase; IRF, interferon response factor; ko, knockout; LMC, large mononuclear cell; L-NMMA, NG-monomethyl-L-arginine; NO, nitric oxide; p.o., peroral; RNI, reactive nitrogen intermediates; ROI, reactive oxygen intermediates; SMC, small mononuclear cell; STAg, soluble tachyzoite antigen.

Dr. Scharton-Kersten and Dr. Yap made equally significant contributions.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS