The IRG proteins: a function in search of a mechanism.

The IRG proteins (p47 GTPases) constitute one of the strongest resistance systems known to be active against intracellular pathogens in mice. The proteins are induced by interferons and assemble on phagosomes and parasitophorous vacuoles of a number of different micro-organisms in all cell types assayed. There are presently three experimentally based views as to how they exert their cell-autonomous activity against intracellular pathogens: blocking of interferon-mediated acceleration of phagosome maturation, induction of autophagic membranes, and direct destruction of the parasitophorous vacuole membrane. Failure of hemopoietic stem cells during infection is associated with targeted deletion of one IRG protein, Irgm1. The significance of this non-cell-autonomous phenotype is discussed.