Summary of cellular and systemic consequences of IRGM knock-outs.

This table summarizes the arguments presented, documented, and referenced in the accompanying article. Each panel can be read from top to bottom as a causal chain. Thus, Irgm1 deficiency results in incomplete regulation of induced effector GKS IRG proteins, which results in build up of cytosolic aggregates, and these in turn have cytopathic consequences. For Irgm1 deficiency, the causal chain is long and ends up with major systemic and cell-autonomous immunodeficiency. In wild-type cells, the causal chain is adaptive and leads to increased cell-autonomous immune competence, while in the Irgm1/Irgm3 double-deficient cells the causal chain heading towards cytopathy is truncated by the rapid clearance of the IRG protein aggregates. The consequences of Irgm1 deficiency are cellular as well as systemic and result in whole-animal immune failure.aThe range of pathogens genuinely controlled by the IRG system of mice is unclear. At present, T. gondii and C. trachomatis stand out, but it is not known what these two pathogens have in common that renders them susceptible to IRG-mediated immunity, nor what the other organisms lack or possess that renders them resistant.