Intracellular pathogenic bacteria, such as Salmonella, evade the immune response by hiding inside vacuoles of macrophages to ensure replication and survival. A new study uncovers a family of GTPases induced by interferon that destroy these hiding places so that bacteria can be recognized and inflammasome immune complexes can be activated in the host cell (Nature doi:10.1038/nature13157).
Using a mouse model of infection with intracellular bacteria, including Salmonella, Ettiene Meunier and colleagues found that guanylate-binding proteins (GBPs), a class of GTPases, were induced by interferon, which is required for activation of the immune system in infected macrophages. GBPs, particularly GBP2, limited bacterial replication and activated the non-canonical caspase-11 inflammasome, although they were not involved in the detection of the bacteria. The authors found that GBPs are recruited to the vacuole containing the bacteria to induce lysis of the vacuole, resulting in Salmonella release into the cytosol so that immune sensors can recognize the bacterial lipopolysaccharide.
It is still unclear how the vacuoles are lysed or how these GBPs distinguish between vacuoles containing pathogens and those that don't inside macrophages. Modulation of the pathways described in this study could be used to control inflammation during sepsis.
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Pola, C. Destroying Salmonella's camouflage. Nat Med 20, 483 (2014). https://doi.org/10.1038/nm.3581