The Mouse Resistance Protein Irgm1 (LRG-47): A Regulator or an Effector of Pathogen Defense?

The interferon-γ (IFNγ)–inducible IRG proteins are a distinctive cytoplasmic GTPase family encoded by about 20 genes in the C57BL/6 mouse [1]. All four IRG genes that have been knocked out (Irgm1, Irgm3, Irgd, Irga6) have caused more or less striking susceptibility phenotypes to Toxoplasma gondii ([2], [3] and O. Liesenfeld, I. Parvanova, J. Zerrahn, S-J. Han, F. Heinrich, et al., unpublished data). However, one single member of the IRG family, Irgm1 (formerly called LRG-47), stands out because it has additionally been implicated in a remarkable range of resistances in the mouse: resistance to Trypanosoma cruzi [4], Leishmania major [5], Listeria monocytogenes [2], Mycobacterium tuberculosis [6], Mycobacterium avium [7], Chlamydia trachomatis [8], and Salmonella typhimurium [9]. These are all intracellular but otherwise very different organisms—some are protozoa, some Gram-negative bacteria, some Gram-positive, some living inside a vacuole or phagosome, and some free in the cytosol. Thus, Irgm1 appears to have exceptional properties of disease resistance not shared by other members of the IRG family.