Inactivation of LRG-47 and IRG-47 reveals a family of interferon gamma-inducible genes with essential, pathogen-specific roles in resistance to infection.

Published

Journal Article

The cytokine interferon (IFN)-gamma regulates immune clearance of parasitic, bacterial, and viral infections; however, the underlying mechanisms are poorly understood. Recently, a family of IFN-gamma-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.

Full Text

Duke Authors

Cited Authors

  • Collazo, CM; Yap, GS; Sempowski, GD; Lusby, KC; Tessarollo, L; Vande Woude, GF; Sher, A; Taylor, GA

Published Date

  • July 2001

Published In

Volume / Issue

  • 194 / 2

Start / End Page

  • 181 - 188

PubMed ID

  • 11457893

Pubmed Central ID

  • 11457893

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.194.2.181

Language

  • eng