Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 159K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Collazo, C. M. Articles by Taylor, G. A. Search for Related Content PubMed PubMed Citation Articles by Collazo, C. M. Articles by Taylor, G. A. Social Bookmarking                            What's this?

Original Article

Inactivation of Lrg-47 and Irg-47 Reveals a Family of Interferon –Inducible Genes with Essential, Pathogen-Specific Roles in Resistance to Infection

^a Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
^b Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912
^c Department of Medicine, Division of Rheumatology, Allergy and Clinical Immunology, Duke University, Durham, NC 27710
^d Department of Medicine and Department of Immunology, Division of Geriatrics, and Center for the Study of Aging and Human Development, Duke University, Durham, NC 27710
^e Geriatric Research, Education, and Clinical Center, VA Medical Center, Durham, NC 27705
^f Division of Basic Sciences, National Cancer Institute, Frederick, MD 21702
^g Van Andel Research Institute, Grand Rapids, MI 49503
Duke University Medical Center, P.O. Box 3003, Durham, NC 27710.919-286-6823919-286-0411 ext. 1-7744

gregory.taylor{at}duke.edu

The cytokine interferon (IFN)- regulates immune clearance of parasitic, bacterial, and viral infections; however, the underlying mechanisms are poorly understood. Recently, a family of IFN-–induced genes has been identified that encode 48-kD GTP-binding proteins that localize to the endoplasmic reticulum of cells. The prototype of this family, IGTP, has been shown to be required for host defense against acute infections with the protozoan parasite Toxoplasma gondii, but not for normal clearance of the bacterium Listeria monocytogenes and murine cytomegalovirus (MCMV). To determine whether other members of the gene family also play important roles in immune defense, we generated mice that lacked expression of the genes LRG-47 and IRG-47, and examined their responses to representative pathogens. After infection with T. gondii, LRG-47–deficient mice succumbed uniformly and rapidly during the acute phase of the infection; in contrast, IRG-47–deficient mice displayed only partially decreased resistance that was not manifested until the chronic phase. After infection with L. monocytogenes, LRG-47–deficient mice exhibited a profound loss of resistance, whereas IRG-47–deficient mice exhibited completely normal resistance. In addition, both strains displayed normal clearance of MCMV. Thus, LRG-47 and IRG-47 have vital, but distinct roles in immune defense against protozoan and bacterial infections.

Key Words: interferon • GTPase • protozoa • bacteria • virus

© 2001 The Rockefeller University Press

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

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS